drug tolerance

Summary

Summary: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.

Top Publications

  1. pmc Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism
    Kristin N Adams
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell 145:39-53. 2011
  2. pmc Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain
    Christian Zöllner
    Klinik fur Anaesthesiologie und operative Intensivmedizin, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
    J Clin Invest 118:1065-73. 2008
  3. pmc ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma
    R R Singh
    Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 30:4874-86. 2011
  4. pmc Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions
    D J Mayer
    Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    Proc Natl Acad Sci U S A 96:7731-6. 1999
  5. ncbi Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence
    L M Bohn
    Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 408:720-3. 2000
  6. ncbi The role of spinal neuroimmune activation in morphine tolerance/hyperalgesia in neuropathic and sham-operated rats
    Vasudeva Raghavendra
    Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA
    J Neurosci 22:9980-9. 2002
  7. ncbi Persister cells and the riddle of biofilm survival
    K Lewis
    Northeastern University, Boston, MA 02115, USA
    Biochemistry (Mosc) 70:267-74. 2005
  8. ncbi Do opioids induce hyperalgesia in humans? An evidence-based structured review
    David A Fishbain
    Department of Psychiatry, Miller School of Medicine at the University of Miami, Florida 33136, USA
    Pain Med 10:829-39. 2009
  9. pmc Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae
    P O Mireji
    Department of Biochemistry and Molecular Biology, Egerton University, Njoro, Kenya
    Med Vet Entomol 24:101-7. 2010
  10. ncbi The involvement of glial cells in the development of morphine tolerance
    P Song
    Shanghai Institute of Physiology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, PR China
    Neurosci Res 39:281-6. 2001

Detail Information

Publications274 found, 100 shown here

  1. pmc Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism
    Kristin N Adams
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Cell 145:39-53. 2011
    ..when Mycobacterium tuberculosis infects cultured macrophages, suggesting that it contributes to the burden of drug tolerance in human tuberculosis. Efflux pump inhibitors like verapamil reduce this tolerance...
  2. pmc Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain
    Christian Zöllner
    Klinik fur Anaesthesiologie und operative Intensivmedizin, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
    J Clin Invest 118:1065-73. 2008
    ....
  3. pmc ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma
    R R Singh
    Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 30:4874-86. 2011
    ....
  4. pmc Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions
    D J Mayer
    Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    Proc Natl Acad Sci U S A 96:7731-6. 1999
    ..This knowledge may also provide a scientific basis for improved pain management with opiate analgesics...
  5. ncbi Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence
    L M Bohn
    Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 408:720-3. 2000
    ..However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug...
  6. ncbi The role of spinal neuroimmune activation in morphine tolerance/hyperalgesia in neuropathic and sham-operated rats
    Vasudeva Raghavendra
    Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA
    J Neurosci 22:9980-9. 2002
    ..Targeting central cytokine production and glial activation may improve the effectiveness of morphine and reduce the incidence of morphine withdrawal-induced hyperalgesia and allodynia in neuropathic pain conditions...
  7. ncbi Persister cells and the riddle of biofilm survival
    K Lewis
    Northeastern University, Boston, MA 02115, USA
    Biochemistry (Mosc) 70:267-74. 2005
    ..Persisters are essentially altruistic cells that forfeit propagation in order to ensure survival of kin cells in the presence of lethal factors...
  8. ncbi Do opioids induce hyperalgesia in humans? An evidence-based structured review
    David A Fishbain
    Department of Psychiatry, Miller School of Medicine at the University of Miami, Florida 33136, USA
    Pain Med 10:829-39. 2009
    ..This is a structured evidence-based review for all levels of evidence (all studies and case reports) on OIH in humans in order to determine the consistency of this evidence...
  9. pmc Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae
    P O Mireji
    Department of Biochemistry and Molecular Biology, Egerton University, Njoro, Kenya
    Med Vet Entomol 24:101-7. 2010
    ..Our results suggest that although An. gambiae s.s. displays the potential to develop tolerance to heavy metals, particularly copper, this may occur at a significant biological cost, which can adversely affect its ecological fitness...
  10. ncbi The involvement of glial cells in the development of morphine tolerance
    P Song
    Shanghai Institute of Physiology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, PR China
    Neurosci Res 39:281-6. 2001
    ..The present investigation provides the first evidence for the role of glial cells in the development of morphine tolerance in vivo...
  11. ncbi Role of delivery and trafficking of delta-opioid peptide receptors in opioid analgesia and tolerance
    Xu Zhang
    Institute of Neuroscience, Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Trends Pharmacol Sci 27:324-9. 2006
    ..Thus, the delivery and trafficking of DOP receptors are crucial processes that modulate opioid analgesia and tolerance...
  12. ncbi Etanercept restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in morphine-tolerant rats
    Ching Hui Shen
    Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
    Anesth Analg 112:454-9. 2011
    ..In the present study we examined the effect of the tumor necrosis factor (TNF)-α antagonist etanercept on the antinociceptive effect of morphine in morphine-tolerant rats...
  13. pmc Mechanisms of rapid opioid receptor desensitization, resensitization and tolerance in brain neurons
    Vu C Dang
    Department of Psychiatry, University of California, San Francisco, CA, USA
    Br J Pharmacol 165:1704-16. 2012
    ..Better understanding of how chronic exposure to opioids alters receptor regulatory mechanisms may facilitate the development of effective analgesics that produce limited tolerance...
  14. ncbi Basic pharmacologic mechanisms involved in benzodiazepine tolerance and withdrawal
    A N Bateson
    Department of Pharmacology, Division of Neuroscience, University of Alberta, Edmonton, Canada
    Curr Pharm Des 8:5-21. 2002
    ..The molecular effects of long-term benzodiazepine exposure are reviewed and a model is presented that draws on results from a number of research groups working in this area...
  15. ncbi Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users
    J G Ramaekers
    Department of Neuropsychology and Psychopharmacology, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands
    J Psychopharmacol 23:266-77. 2009
    ..These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC...
  16. pmc RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia
    Frederic Simonin
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université Louis Pasteur, 67404 Illkirch Cedex, France
    Proc Natl Acad Sci U S A 103:466-71. 2006
    ..Our data indicate that NPFF receptors are part of a bona fide antiopioid system and that selective antagonists of these receptors could represent useful therapeutic agents for improving the efficacy of opioids in chronic pain treatment...
  17. ncbi Cellular and synaptic adaptations mediating opioid dependence
    J T Williams
    Vollum Institute, Oregon Health Sciences University, Portland, Oregon, USA
    Physiol Rev 81:299-343. 2001
    ..The characterization of common pathways affected by different drugs, particularly after repeated treatment, is important in the understanding of drug abuse...
  18. ncbi A novel role of minocycline: attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia
    Yu Cui
    Department of Physiology, Zhongshan Medical College, Sun Yat Sen University, Guangzhou 510080, PR China
    Brain Behav Immun 22:114-23. 2008
    ..To our knowledge, this is the first study to demonstrate that minocycline antagonizes morphine antinociceptive tolerance, possibly due to the inhibition of p38 activation in the spinal microglia...
  19. ncbi Overexpression of monodehydroascorbate reductase in transgenic tobacco confers enhanced tolerance to ozone, salt and polyethylene glycol stresses
    Amin Elsadig Eltayeb
    Laboratory of Plant Biotechnology, Faculty of Agriculture, Tottori University, Koyama, Tottori 680 8553, Japan
    Planta 225:1255-64. 2007
    ..These results demonstrate that an overexpressed level of MDAR properly confers enhanced tolerance against ozone, salt and PEG stress...
  20. ncbi Activation of TRPV1 contributes to morphine tolerance: involvement of the mitogen-activated protein kinase signaling pathway
    Yong Chen
    Department of Neurology, University of Wurzburg, 97080 Wurzburg, Germany
    J Neurosci 28:5836-45. 2008
    ..Thus, blocking TRPV1 might be a way to reduce morphine tolerance...
  21. ncbi A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine
    Ian N Johnston
    Department of Psychology, University of Colorado, Boulder, Colorado 80309, USA
    J Neurosci 24:7353-65. 2004
    ..Taken together, these results suggest that IL-1 and fractalkine are endogenous regulators of morphine analgesia and are involved in the increases in pain sensitivity that occur after chronic opiates...
  22. ncbi Bacterial persistence as a phenotypic switch
    Nathalie Q Balaban
    Laboratory of Living Matter and Center for Studies in Physics and Biology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 305:1622-5. 2004
    ..Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections...
  23. ncbi Neurobiological evidence for hedonic allostasis associated with escalating cocaine use
    Serge H Ahmed
    Laboratoire de Neuropsychobiologie des Desadaptations, Universite de Bordeaux 2, CNRS UMR 5541, 146 rue Leo Saignat, Bordeaux 33076, France
    Nat Neurosci 5:625-6. 2002
    ....
  24. ncbi Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena
    Robert M Post
    Penn State College of Medicine, 3502 Turner Lane, Chevy Chase, MD 20815, USA
    Neurosci Biobehav Rev 31:858-73. 2007
    ....
  25. ncbi Ethanol tolerance caused by slowpoke induction in Drosophila
    Roshani B Cowmeadow
    Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 78712 0248, USA
    Alcohol Clin Exp Res 30:745-53. 2006
    ..In Drosophila, induction of slowpoke expression has been linked to anesthetic resistance...
  26. pmc BK channels play a counter-adaptive role in drug tolerance and dependence
    Alfredo Ghezzi
    Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 107:16360-5. 2010
    ..These data provide a possible mechanism for the long-standing counter-adaptive theory for drug tolerance in which homeostatic adaptations triggered by drug exposure to produce drug tolerance become counter-adaptive ..
  27. ncbi Role of receptor internalization in opioid tolerance and dependence
    Thomas Koch
    Department of Pharmacology and Toxicology, Otto von Guericke University, 39120 Magdeburg, Germany
    Pharmacol Ther 117:199-206. 2008
    ..Thus, clearer understanding of the role of opioid receptor trafficking in the regulation of opioid tolerance and dependence will help in the treatment of patients suffering from chronic pain or drug dependence...
  28. ncbi The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence
    Lene Martini
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St Suite 200, Emeryville, CA 94608, United States
    Curr Opin Neurobiol 17:556-64. 2007
    ..As a consequence, facilitating receptor endocytosis, using either genetic or pharmacological approaches, can restore the balance of signaling through the receptor and affect the development of tolerance and dependence...
  29. pmc Drug-induced epigenetic changes produce drug tolerance
    Yan Wang
    Section of Neurobiology, The University of Texas at Austin, Austin, Texas, USA
    PLoS Biol 5:e265. 2007
    ..These findings provide unique evidence that links molecular epigenetic histone modifications and transcriptional induction of an ion channel gene with a single behavioral event...
  30. pmc Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli
    D G White
    Center for Adaptation Genetics and Drug Resistance and Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Bacteriol 179:6122-6. 1997
    ..These findings strongly suggest that active efflux specified by the acrAB locus is linked to intrinsic organic solvent tolerance and to tolerance mediated by the marA, soxS, or robA gene product in E. coli...
  31. ncbi Proteomic analysis of spinal protein expression in rats exposed to repeated intrathecal morphine injection
    Hao Ai Shui
    Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
    Proteomics 7:796-803. 2007
    ..It is very likely that these identified proteins may serve as potential molecular targets for prevention of the development of morphine tolerance and physical dependence...
  32. ncbi Pharmacology of methadone and its isomers
    C E Inturrisi
    Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Minerva Anestesiol 71:435-7. 2005
    ..Thus, the same dose of intrathecal d-methadone that attenuates the development of spinal morphine tolerance blocks NMDA-induced hyperalgesia in rats. These results support the..
  33. ncbi Homeostatic control of neural activity: a Drosophila model for drug tolerance and dependence
    Alfredo Ghezzi
    Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology, The University of Texas at Austin, 1 University Station C0920, Austin Texas 78712 0248, USA
    Int Rev Neurobiol 99:23-50. 2011
    ..b>Drug tolerance is a measurable endophenotype of addiction that can be easily generated and detected in animal models...
  34. pmc slo K(+) channel gene regulation mediates rapid drug tolerance
    Alfredo Ghezzi
    Section of Neurobiology, University of Texas, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 101:17276-81. 2004
    ..with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage between these two phenomena by using a mutation and a transgene...
  35. ncbi The Mycobacterium tuberculosis iniA gene is essential for activity of an efflux pump that confers drug tolerance to both isoniazid and ethambutol
    Roberto Colangeli
    Division of Infectious Disease and the Center for Emerging Pathogens, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA
    Mol Microbiol 55:1829-40. 2005
    ..Drugs designed to inhibit the iniA gene product may shorten the time required to treat tuberculosis and may help prevent the clinical emergence of drug resistance...
  36. ncbi Opioid-induced hyperalgesia and tolerance
    Mary Hanna Bekhit
    Department of Anesthesiology, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, Los Angeles, CA 90095, USA
    Am J Ther 17:498-510. 2010
    ....
  37. pmc Morphine tolerance attenuates the resolution of postoperative pain and enhances spinal microglial p38 and extracellular receptor kinase phosphorylation
    R J Horvath
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Neuroscience 169:843-54. 2010
    ....
  38. ncbi Chronic benzodiazepine treatment of cells expressing recombinant GABA(A) receptors uncouples allosteric binding: studies on possible mechanisms
    N J Ali
    Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1735, USA
    J Neurochem 79:1100-8. 2001
    ..The internalization of receptors was shown by immunofluorescence after chronic exposure to either BZ or the PKA inhibitor H-89...
  39. ncbi Gene knockdown with lentiviral vector-mediated intrathecal RNA interference of protein kinase C gamma reverses chronic morphine tolerance in rats
    Zongbin Song
    Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
    J Gene Med 12:873-80. 2010
    ....
  40. ncbi Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study
    T Gori
    Division of Cardiology, Department of Medicine, Mount Sinai Hospital, and the University of Toronto, Toronto, Canada
    Circulation 104:1119-23. 2001
    ..We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our results confirm the view that oxidative stress contributes to nitrate tolerance...
  41. ncbi Morphine-induced analgesic tolerance, locomotor sensitization and physical dependence do not require modification of mu opioid receptor, cdk5 and adenylate cyclase activity
    Candice Contet
    département de neurobiologie, IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U596, CNRS UMR7104, Universite Louis Pasteur, 1 rue Laurent Fries, F 67400 Illkirch, France
    Neuropharmacology 54:475-86. 2008
    ....
  42. pmc Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction
    M J Christie
    Pain Management Research Institute and Kolling Institute, University of Sydney, Royal North Shore Hospital, St Leonards, NSW, Australia
    Br J Pharmacol 154:384-96. 2008
    ....
  43. pmc N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma
    Takeaki Kudo
    Department of General Surgery, Graduate School of Medicine, Hokkaido University, Japan
    Mol Cancer 6:32. 2007
    ..Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood...
  44. pmc Proteomic analysis reveals the participation of energy- and stress-related proteins in the response of Pseudomonas putida DOT-T1E to toluene
    Ana Segura
    EEZ CSIC, C Prof Albareda, 1, E 18008 Granada, Spain
    J Bacteriol 187:5937-45. 2005
    ....
  45. ncbi New approaches to study the development of morphine tolerance and dependence
    Hiroshi Ueda
    Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1 14 Bunkyo machi, 852 8521, Nagasaki, Japan
    Life Sci 74:313-20. 2003
    ....
  46. ncbi Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance
    Yehuda Shavit
    Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel
    Pain 115:50-9. 2005
    ..These findings suggest that morphine produces an IL-1-mediated homeostatic response, which serves to limit the duration and extent of morphine analgesia and which underlies the development of tolerance...
  47. pmc How to design an opioid drug that causes reduced tolerance and dependence
    Amy Chang Berger
    Department of Neurology, University of California, San Francisco, Ernest Gallo Clinic and Research Center, Emeryville, CA, USA
    Ann Neurol 67:559-69. 2010
    ..We also discuss preliminary evidence that heteromers of the delta opioid receptor and the MOR are pronociceptive, and that drugs that spare such heteromers may also induce reduced tolerance...
  48. ncbi Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence
    J G Liu
    Department of Pharmacology, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA
    Brain Res Brain Res Rev 38:1-19. 2001
    ..Clearer understanding of the molecular mechanisms of opioid tolerance and dependence will help in the treatment of patients suffering from acute and chronic pain, or drug dependence and addiction...
  49. pmc Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence
    Joseph A Kim
    Ernest Gallo Clinic and Research Center, 5858 Horton St, Suite 200, Emeryville, California 94608, USA
    Curr Biol 18:129-35. 2008
    ..These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence...
  50. ncbi Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study
    W Ma
    Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada H4H 1R3
    Eur J Neurosci 14:1091-104. 2001
    ....
  51. ncbi Tolerance and stress response to ethanol in the yeast Saccharomyces cerevisiae
    Junmei Ding
    Laboratory for Conservation and Utilization of Bio Resources, and Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan 650091, China
    Appl Microbiol Biotechnol 85:253-63. 2009
    ..Here, we review the recent progresses in our understanding of ethanol resistance and stress responses in yeast...
  52. ncbi Opioid tolerance and hyperalgesia
    Grace Chang
    Massachusetts General Hospital Pain Center, Division of Pain Medicine, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Med Clin North Am 91:199-211. 2007
    ..This article will review updated information from both clinical and preclinical studies regarding opioid-induced hyperalgesia, tolerance, and dependence. The implications of these issues in clinical opioid therapy also will be discussed...
  53. ncbi Pharmacogenetics of antidepressant medication intolerance
    Greer M Murphy
    Neruroscience Research Laboratories Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford CA 94305 5548, USA
    Am J Psychiatry 160:1830-5. 2003
    ..However, variation in genes encoding serotonin receptors could also explain antidepressant side effects (pharmacodynamic effect)...
  54. ncbi Role for peroxynitrite in the inhibition of prostacyclin synthase in nitrate tolerance
    Ulrich Hink
    University Hospital Eppendorf, Division of Cardiology, Hamburg, Germany
    J Am Coll Cardiol 42:1826-34. 2003
    ..We tested whether in vivo nitroglycerin (NTG) treatment causes tyrosine nitration of prostacyclin synthase (PGI(2)-S), one of the nitration targets of peroxynitrite, and whether this may contribute to nitrate tolerance...
  55. ncbi Hydralazine is a powerful inhibitor of peroxynitrite formation as a possible explanation for its beneficial effects on prognosis in patients with congestive heart failure
    Andreas Daiber
    Klinikum der Johannes Gutenberg Universitat, II Medizinische Klinik und Poliklinik, Labor für Molekulare Kardiologie, 55101 Mainz, Germany
    Biochem Biophys Res Commun 338:1865-74. 2005
    ....
  56. ncbi Receptor endocytosis counteracts the development of opioid tolerance
    Thomas Koch
    Department of Pharmacology and Toxicology, Otto von Guericke University, 39120 Magdeburg, Leipziger Strasse 44, Germany
    Mol Pharmacol 67:280-7. 2005
    ..Our findings suggest that opioids with high endocytotic efficacies might cause reduced opioid tolerance but can facilitate compensatory mechanisms, resulting in an enhanced opioid dependence...
  57. pmc Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients
    Markus Moehler
    1st Medical Department, Johannes Gutenberg University, Langenbeckstrasse 1, 55116 Mainz, Germany
    World J Gastroenterol 15:449-56. 2009
    ..To investigate the efficacy and safety of cape-citabine plus irinotecan +/- bevacizumab in advanced or metastatic colorectal cancer patients...
  58. ncbi Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization
    Li He
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA
    Cell 108:271-82. 2002
    ..These results demonstrate that endocytosis of the MOR can reduce the development of tolerance, and hence suggest an approach for the development of opiate analogs with enhanced efficacy for the treatment of chronic pain...
  59. ncbi Genetic variation in morphine analgesic tolerance: a survey of 11 inbred mouse strains
    Benjamin Kest
    Department of Psychology and Center for Developmental Neuroscience, The College of Staten Island, City University of New York, Staten Island, NY 10314, USA
    Pharmacol Biochem Behav 73:821-8. 2002
    ..The present work demonstrates that the presence and magnitude of morphine analgesic tolerance is genotype-dependent and identifies strains with widely divergent liabilities that should facilitate identification of trait-relevant genes...
  60. ncbi The slowpoke gene is necessary for rapid ethanol tolerance in Drosophila
    R B Cowmeadow
    Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas 78712 0248, USA
    Alcohol Clin Exp Res 29:1777-86. 2005
    ..Recently, the slowpoke BK-type calcium-activated potassium channel gene has been shown to be involved in ethanol sensitivity in Caenorhabditis elegans and in rapid tolerance to the anesthetic benzyl alcohol in Drosophila...
  61. ncbi Sex-specific responses to opiates: animal and human studies
    Albert Dahan
    Department of Anesthesiology, Leiden University Medical Center, P5 Q, 2300 RC Leiden, The Netherlands
    Anesth Analg 107:83-95. 2008
    ....
  62. pmc Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice
    Carolina Muscoli
    Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Catanzaro, Italy
    J Clin Invest 117:3530-9. 2007
    ..Peroxynitrite (ONOO-) decomposition catalysts may have therapeutic potential as adjuncts to opiates in relieving suffering from chronic pain...
  63. ncbi The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance
    Jean Paul Laulin
    Universite Bordeaux 1, France
    Anesth Analg 94:1263-9, table of contents. 2002
    ..Although ketamine had no analgesic effect per se at the dose used herein, our results indicate that sustained NMDA-receptor blocking could be a fruitful therapy for improving postoperative morphine effectiveness...
  64. ncbi Transition from moderate to excessive drug intake: change in hedonic set point
    S H Ahmed
    Division of Psychopharmacology, Department of Neuropharmacology, CVN 7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 282:298-300. 1998
    ..After 1 month of abstinence, escalation of cocaine intake was reinstated to a higher level than before. These findings may provide an animal model for studying the development of excessive drug intake and the basis of addiction...
  65. pmc Ligand-directed trafficking of the δ-opioid receptor in vivo: two paths toward analgesic tolerance
    Amynah A A Pradhan
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Institut National de la Santé et de la Recherche Médicale Université de Strasbourg, 67404 Illkirch, France
    J Neurosci 30:16459-68. 2010
    ..Hence, ligand-directed receptor trafficking of the δ-opioid receptor engages distinct adaptive responses, and this study reveals a novel aspect of biased agonism in vivo...
  66. ncbi Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats
    Vasudeva Raghavendra
    Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
    Neuropsychopharmacology 29:327-34. 2004
    ..These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity...
  67. pmc Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance
    Karsten Sydow
    The University Hospital Eppendorf, Division of Cardiology, Hamburg, Germany
    J Clin Invest 113:482-9. 2004
    ..Thus, GTN tolerance may be viewed as a metabolic syndrome characterized by mitochondrial dysfunction...
  68. ncbi RGS proteins: new players in the field of opioid signaling and tolerance mechanisms
    Guo Xi Xie
    Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Avenue, Box 0464, Room S 455, San Francisco, CA 94143, USA
    Anesth Analg 100:1034-42. 2005
    ..Using RGS proteins as targets for future drug therapy aimed at modulating opioid effectiveness in both acute and chronic pain settings may be an important advance in the treatment of pain...
  69. ncbi The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence
    Yong Chen
    Center for Translational Neuroscience, Duke University, Durham, NC 27710, USA
    Mol Neurobiol 40:101-7. 2009
    ..In this review, we focus on the current understanding of the role of MAPK signaling pathways in morphine tolerance and dependence...
  70. ncbi An opiate cocktail that reduces morphine tolerance and dependence
    Li He
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA
    Curr Biol 15:1028-33. 2005
    ..We further demonstrate that dependence is reduced, at least in part, because endocytosis of the MOP receptor in response to morphine prevents the upregulation of N-methyl-D-aspartate (NMDA) receptors...
  71. ncbi Functional and biochemical analysis of endothelial (dys)function and NO/cGMP signaling in human blood vessels with and without nitroglycerin pretreatment
    Eberhard Schulz
    University Hospital Eppendorf, Division of Cardiology, Hamburg, Germany
    Circulation 105:1170-5. 2002
    ..However, it is still controversial whether nitrate tolerance in humans is associated with both endothelial dysfunction and impaired vascular response to nitrovasodilator-derived NO...
  72. ncbi Persister cells and tolerance to antimicrobials
    Iris Keren
    Department of Biology, Northeastern University, Boston, MA 02115, USA
    FEMS Microbiol Lett 230:13-8. 2004
    ..This suggests that persisters are not at a particular stage in the cell cycle, neither are they defective cells nor cells created in response to antibiotics. Our data indicate that persisters are specialized survivor cells...
  73. ncbi Rapid onset of tolerance to beta-agonist bronchodilation
    Sarah Haney
    Department of Respiratory Medicine, Waikato Hospital, Hamilton, New Zealand
    Respir Med 99:566-71. 2005
    ..This is easily demonstrated if dilation is tested following methacholine challenge. It is not known how quickly tolerance develops or how long it lasts after stopping beta-agonist therapy...
  74. pmc Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance
    L J Sim-Selley
    Department of Pharmacology and Toxicology, Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Medical College of Virginia Campus, 1112 East Clay Street, Richmond, VA 23298, USA
    Br J Pharmacol 151:1324-33. 2007
    ..The present study examined MOR-mediated G-protein activation in the CNS of mice with different levels of morphine tolerance...
  75. ncbi Remifentanil and cyclooxygenase inhibitors interactions in the minimum alveolar concentration of sevoflurane in the rat
    J Benito
    Department of Animal Medicine and Surgery, Veterinary Faculty, Universidad Complutense, Madrid, Spain
    Br J Anaesth 105:810-7. 2010
    ..Our aim was to determine whether COX inhibitors potentiate the effect of remifentanil on the minimum alveolar concentration (MAC) of sevoflurane anaesthetized rats...
  76. ncbi mu-Opioid receptor downregulation contributes to opioid tolerance in vivo
    K Stafford
    Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA
    Pharmacol Biochem Behav 69:233-7. 2001
    ..Therefore, opioid tolerance appears to rely upon both "receptor density-dependent" and " receptor density-independent" mechanisms...
  77. ncbi Co-administration of ultra-low dose naloxone attenuates morphine tolerance in rats via attenuation of NMDA receptor neurotransmission and suppression of neuroinflammation in the spinal cords
    Shinn Long Lin
    Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan
    Pharmacol Biochem Behav 96:236-45. 2010
    ..These findings demonstrated that attenuation of glutamatergic transmission and neuroinflammation by ultra-low dose naloxone co-infusion preserves the lasting antinociceptive effect of morphine in rats chronically infused with morphine...
  78. pmc CREB regulation of BK channel gene expression underlies rapid drug tolerance
    Y Wang
    Section of Neurobiology, The University of Texas at Austin, Austin, TX 78712 0248, USA
    Genes Brain Behav 8:369-76. 2009
    ..These findings suggest that CREB positively regulates the expression of slo-encoded BK-type Ca(2+)-activated K(+) channels and that this gives rise to behavioral tolerance to benzyl alcohol sedation...
  79. ncbi Interplay between population dynamics and drug tolerance of Staphylococcus aureus persister cells
    Sabrina Lechner
    Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Lehrbereich Mikrobielle Genetik, Eberhard Karls Universitat Tubingen, Tubingen, Germany
    J Mol Microbiol Biotechnol 22:381-91. 2012
    ..aureus persisters. Judging from time-dependent experiments, the persisters' degree of drug tolerance correlated with the duration of antibiotic challenge...
  80. ncbi Overexpression of MSN2 in a sake yeast strain promotes ethanol tolerance and increases ethanol production in sake brewing
    Mamoru Watanabe
    National Research Institute of Brewing, 3 7 1 Kagamiyama, Higashihiroshima 739 0046, Japan
    J Biosci Bioeng 107:516-8. 2009
    ..We showed that this strain is more ethanol tolerant and produced more ethanol in a sake mash than a control strain...
  81. ncbi Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice
    B Habibi-asl
    Department of Pharmacology and Toxicology, School of Pharmacy, Tabriz University Medical Sciences, Tabriz, Iran
    Pak J Biol Sci 12:798-803. 2009
    ....
  82. ncbi Neural mechanisms of tolerance to the effects of cocaine
    R P Hammer
    Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA
    Behav Brain Res 84:225-39. 1997
    ....
  83. ncbi Enhancement of the stress response by minute amounts of cadmium in sensitized Reuber H35 hepatoma cells
    F A Wiegant
    Department of Molecular Cell Biology, Utrecht University, The Netherlands
    Toxicology 116:27-37. 1997
    ....
  84. pmc Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons
    Erica S Levitt
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Mol Pharmacol 82:983-92. 2012
    ..This PKC-mediated desensitization may contribute to the previously reported PKC-dependent reversal of behavioral tolerance...
  85. ncbi The effects of gabapentin on acute opioid tolerance to remifentanil under sevoflurane anesthesia in rats
    Delia Aguado
    Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Avda Puerta de Hierro s n, 28040 Madrid, Spain
    Anesth Analg 115:40-5. 2012
    ..We sought to determine whether gabapentin might prevent the observed acute opioid tolerance (AOT) produced by remifentanil in sevoflurane minimum alveolar concentration (MAC)...
  86. pmc Phenotypic tolerance: antibiotic enrichment of noninherited resistance in bacterial populations
    C Wiuff
    Department of Biology, Emory University, 1510 Clifton Rd, Atlanta, Georgia 30322, USA
    Antimicrob Agents Chemother 49:1483-94. 2005
    ....
  87. ncbi Analgesic tolerance to high-efficacy agonists but not to morphine is diminished in phosphorylation-deficient S375A μ-opioid receptor knock-in mice
    Gisela Grecksch
    Institute of Pharmacology and Toxicology, Faculty of Medicine, Otto von Guericke University, D 39120 Magdeburg, Germany
    J Neurosci 31:13890-6. 2011
    ..Whereas tolerance induced by DAMGO or etonitazene requires agonist-driven phosphorylation of S375, the development and maintenance of antinociceptive tolerance to morphine occurs independent of S375 phosphorylation...
  88. ncbi Ketamine and remifentanil interactions on the sevoflurane minimum alveolar concentration and acute opioid tolerance in the rat
    Delia Aguado
    Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Avda, Puerta de Hierro s n, 28040 Madrid, Spain
    Anesth Analg 113:505-12. 2011
    ..In this study we determined the interaction of ketamine and remifentanil on the minimum alveolar concentration (MAC) of sevoflurane in rats and to determine whether ketamine may block acute opioid tolerance (AOT)...
  89. ncbi Vigabatrin attenuates the development and expression of tolerance to morphine-induced antinociception in mice
    Behzad Chavooshi
    Department of Psychology, Faculty of Psychology and Education, University of Tehran, Tehran, Iran
    Pharmacol Biochem Behav 93:155-9. 2009
    ..Additionally, VGB alone did not affect the tail-flick latency times. Therefore, while VGB alone has no antinociceptive effect, it can prevent the development of morphine tolerance in mice...
  90. ncbi Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice
    Ahmed O Abdel-Zaher
    Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt
    Neurochem Res 35:1557-65. 2010
    ..These results provide evidence that Nigella sativa oil, through inhibition of morphine-induced NO overproduction and oxidative stress, appears to have a therapeutic potential in opioid tolerance and dependence...
  91. ncbi Spinal cord neuroplasticity following repeated opioid exposure and its relation to pathological pain
    J Mao
    MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
    Ann N Y Acad Sci 933:175-84. 2001
    ..These observations may help understand mechanisms of chemical intolerance and multiple chemical sensitivity as well as have significant clinical implications in pain management with opioid analgesics...
  92. ncbi Requirement of alpha5-GABAA receptors for the development of tolerance to the sedative action of diazepam in mice
    Carolien van Rijnsoever
    Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland
    J Neurosci 24:6785-90. 2004
    ..Thus, the chronic activation of alpha(5)-GABA(A) receptors is crucial for the normal development of sedative tolerance to diazepam, which manifests itself in conjunction with alpha1-GABA(A) receptors...
  93. pmc Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats
    M H Zissen
    Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA
    Neuroscience 144:247-62. 2007
    ..Furthermore, tolerance, opioid-induced hypersensitivity, and withdrawal-associated hypersensitivity are age-specific and may be mediated by distinct mechanisms...
  94. ncbi Assessing cognitive functioning in cannabis users: cannabis use history an important consideration
    Benjamin R Nordstrom
    Neuropsychopharmacology 31:2798-9; author reply 2800-1. 2006
  95. ncbi Transposon mutagenesis identifies genes which control antimicrobial drug tolerance in stationary-phase Escherichia coli
    Yanmin Hu
    Department of Medical Microbiology, St George s Hospital Medical School, London SW17 ORE, UK
    FEMS Microbiol Lett 243:117-24. 2005
    ..coli. Furthermore, they show that it is important in murine infection during antibiotic treatment and lead to a faster kill of the mutant bacteria...
  96. pmc Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli
    Frederick F Correia
    Department of Biology, Northeastern University, 405 Mugar Hall, 360 Huntington Avenue, Boston, MA 02115, USA
    J Bacteriol 188:8360-7. 2006
    ..Taken together, these results suggest that the protein kinase activity of HipA is essential for persister formation...
  97. ncbi Time-course data analysis of gene expression profiles reveals purR regulon concerns in organic solvent tolerance in Escherichia coli
    Kazunori Shimizu
    Department of Biotechnology, School of Engineering, Nagoya University, Furo cho, Chikusa ku, Nagoya 464 8603, Japan
    J Biosci Bioeng 99:72-4. 2005
    ..It was found that the purR regulon plays an important role in the organic solvent tolerance (OST) of E. coli...
  98. ncbi Prolonged exposure to the candidate microbicide C31G differentially reduces cellular sensitivity to agent re-exposure
    Bradley J Catalone
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
    Biomed Pharmacother 59:460-8. 2005
    ....
  99. ncbi The effect of chronic lorazepam administration in aging mice
    Jeanne M Fahey
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and the Division of Clinical Pharmacology, Tufts New England Medical Center, Boston, MA 02111, USA
    Brain Res 1118:13-24. 2006
    ....
  100. ncbi mu-Opioid receptor down-regulation and cAMP-dependent protein kinase phosphorylation in a mouse model of chronic morphine tolerance
    M A Bernstein
    Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    Brain Res Mol Brain Res 55:237-42. 1998
    ....
  101. pmc Activation of protein kinase C (PKC)α or PKCε as an approach to increase morphine tolerance in respiratory depression and lethal overdose
    Hong Yiou Lin
    Department of Pharmacology, University of Minnesota, 6 120 Jackson Hall, 321 Church St S E, Minneapolis, MN 55455 0217, USA
    J Pharmacol Exp Ther 341:115-25. 2012
    ..The approach of increasing morphine respiratory depression and lethality tolerance by increasing PKCα or ε activity at preBötC could be used to make opioids safer for long-term use...

Research Grants65

  1. Role of transcriptional regulation in Aspergillus fumigatus drug resistance
    W Scott Moye-Rowley; Fiscal Year: 2012
    ..Interference with control of gene expression of drug resistance loci will prevent normal levels of drug tolerance from developing. Increased sensitization of A...
  2. TRP Ca2+ Channels in the Skin
    Haoxing Xu; Fiscal Year: 2013
    ..most anti-EGFR agents cause adverse side effects and are only partially effective due to quickly developed drug tolerance. We seek an alternative and novel strategy to treat EGFR-dependent carcinomas...
  3. Disrupting Biofilm Formation to Improve TB Drug Treatment
    Randall J Basaraba; Fiscal Year: 2013
    ..Similar to what is seen in vivo, our data show that Mtb expresses extreme in vitro drug tolerance, which is reversed by anti-biofilm drugs, rendering bacilli again susceptible to TB drugs...
  4. Prevention of oxidative stress decreases persistence of drug tolerant M. Tubercu
    Randall J Basaraba; Fiscal Year: 2010
    ..Our research is aimed at preventing tissue damage and bacterial persistence so that antibiotics are more effective and the length of time required for patient treatment is reduced. ..
  5. Identifying essential functions in non replicating Mycobacterium tuberculosis
    SARAH S GRANT; Fiscal Year: 2013
    ..in metabolic or regulatory pathways important in other models of non-replication, including a stochastic drug tolerance model, an anaerobic model and a stationary phase model, and that these targets are also important in ..
  6. Trajectory of Adverse events and Analgesia with Opioids in older adults - TAANGO
    Richard A Deyo; Fiscal Year: 2013
    ..We hypothesize that there is initial analgesc benefit that wanes as drug tolerance occurs, but resumes with dose increases...
  7. Genome-wide protein-DNA interactions responding to chronic opioid treatment
    Yulong Chen; Fiscal Year: 2012
    ..in the brain reward, pain, and learning and memory circuits, resulting in neuroadaptations that underlie drug tolerance, physical dependence, and withdrawal (symptoms associated with both physical dependence and motivational ..
  8. A "radical" approach to tuberculosis infection
    Deborah T Hung; Fiscal Year: 2013
    ..The term phenotypic antibiotic tolerance (drug tolerance) is used to describe the reduced efficacy of antibiotics against these bacteria in the absence of genotypic ..
  9. A resource for the genetic analysis of complex traits
    STUART JOHN MACDONALD; Fiscal Year: 2012
    ....
  10. The Role of BK Channel Composition in Alcohol Tolerance and Consumption
    Steven N Treistman; Fiscal Year: 2012
    ..In this proposal, we pursue exciting new data which indicates a role for the BK channel beta4 subunit protein in the control of alcohol tolerance and consumption. ..
  11. Methods for the Development of Arrestin2 Inhibitors.
    Spiro Pavlopoulos; Fiscal Year: 2010
    ..g. cannabis). This downregulation of the GPCR is a factor leading to drug tolerance which is a key issue in understanding addiction...
  12. Advancing the Understanding of Drug-Induced Allostasis
    Douglas S Ramsay; Fiscal Year: 2013
    ..provided by applicant): Chronic drug administration can produce allostasis, a maladaptive state related to drug tolerance. Repeated administrations of nitrous oxide (N2O) lead to a frank intra-administration allostatic ..
  13. Sedation Management in Pediatric Patients with Acute Respiratory Failure
    MARTHA AQ CURLEY; Fiscal Year: 2013
    ..Over time, drug tolerance develops and may precipitate iatrogenic withdrawal syndrome when sedation is no longer necessary...
  14. CRCNS: Automated Behavior Analysis for Model Genetic Organism
    Michael H Dickinson; Fiscal Year: 2010
    ..genetic tools available in this organism have identified a series of candidate genes involved in alcohol and drug tolerance. Recent studies of human populations indicate similar genes may be involved in alcohol addiction...
  15. Biofilm formation in mycobacterial persistence and drug tolerance in vivo
    Lynn E Connolly; Fiscal Year: 2010
    ..This will be the first detailed functional analysis of the role of biofilm formation in mycobacterial persistence in vivo. ..
  16. Drug-Induced Allostasis and Its Motivational Effects During Adolescence
    Douglas S Ramsay; Fiscal Year: 2012
    ..provided by applicant): Chronic drug administration can produce allostasis, a maladaptive state related to drug tolerance. This proposal investigates nitrous oxide (N2O)-induced allostatic changes and the motivational consequences ..
  17. THE BEHAVIORAL PHARMACOLOGY OF PHENCYCLIDINE
    Robert L Balster; Fiscal Year: 2010
    ..have potential as medications for neurological and behavioral disorders, including as treatments for drug tolerance and dependence...
  18. Regulation of Clathrin-Coated Pits by the Mu-Opioid Receptor
    MANOJKUMAR AKKAPPILLIL PUTHENVEEDU; Fiscal Year: 2011
    ..neuronal response to MOR signaling, and affects the long-term cellular changes that lead to the development of drug tolerance and dependence...
  19. CONTROL OF VASCULAR TONE BY CONTINGENT CNS STIMULATION
    Barry Dworkin; Fiscal Year: 2006
    ..Classical conditioning, the most studied neural plasticity, is involved in drug tolerance, digestion, and quantitative adjustment of critical visual tracking reflexes...
  20. Problem-Based Learning for Drug Abuse and Addiction Education
    DINA GROSSMAN MARKOWITZ; Fiscal Year: 2010
    ..modules will be: (1) The effects of addiction on behavior, (2) The effects of addiction on homeostasis: drug tolerance and withdrawal, and (3) The effects of drugs on prenatal and postnatal development...
  21. CLINICAL AND PSYCHOSOCIAL INFLUENCES ON HIV THERAPY
    Richard Rothenberg; Fiscal Year: 1999
    ..g., drug tolerance, longer term side effects, drug resistance) but on economic, cultural, and social factors as well (e.g...
  22. Determinants of Tolerance to Nitrous Oxide Hypothermia
    Karl Kaiyala; Fiscal Year: 2004
    ..Influential theories of drug tolerance contend that CNS-mediated drug-opposing responses underlie the etiology of drug tolerance and dependence...
  23. Nitrous Oxide, Individual Differences, and Conditioning
    Douglas Ramsay; Fiscal Year: 2007
    ..b>Drug tolerance, dependence and withdrawal are thought to be manifestations of a common underlying "adaptive" response that ..
  24. MU & DELTA RECEPTORS--ROLE IN TRANSMISSION & ADDICTION
    Huda Akil; Fiscal Year: 1999
    ..entities to drug responsiveness, and determine changes in expression under conditions which promote drug tolerance versus drug sensitization...
  25. SLEEP HOMEOSTASIS AND STIMULANT DRUGS OF ABUSE
    Emmanuel Mignot; Fiscal Year: 2002
    ..cocaine administration remains uncoupled from the normal sleep homeostatic mechanisms that invoke CSR, and drug tolerance reduces CSR to sleep deprivation during psychostimulant administration...
  26. INDIVIDUAL DIFFERENCES AND ADDICTIVE VULNERABILITY
    Douglas Ramsay; Fiscal Year: 2000
    ..These studies have theoretical importance for understanding the mechanisms of drug tolerance as well as what accounts for individual differences in vulnerability to addiction and drug abuse.
  27. Sedation Management in Pediatric Patients supported on *
    MARTHA CURLEY; Fiscal Year: 2004
    ..Additionally, drug tolerance develops over time and may precipitate iatrogenic abstinence syndrome when the patient no longer requires ..
  28. Neuroadaptive Substrates for Nitrous Oxide Tolerance
    Karl Kaiyala; Fiscal Year: 2006
    ..believe that these adaptive changes give rise to central features of the addiction phenotype, including drug tolerance, dependence and withdrawal...
  29. DENTIST SCIENTIST AWARD--INSTITUTIONAL
    BEVERLY DALE CRUNK; Fiscal Year: 2004
    ..This hypothesis can be extended to account for drug tolerance. Drug tolerance occurs when a drug causes less effect over repeated usage...
  30. PAVLOVIAN MEDIATION OF DRUG SELF-ADMINISTRATION
    Christopher Cunningham; Fiscal Year: 1991
    ..Pavlovian conditioned responses have also been shown to contribute to the growth of drug tolerance. No study, however, has yet shown a direct link between conditioned drug responses and self-administration...
  31. Analysis of Touch Response & Habituation in C. elegans
    William Schafer; Fiscal Year: 2007
    ..and inappropriate activation of these plasticity mechanisms through chronic drug use is thought to underlie drug tolerance and dependence...
  32. MOLECULAR/GENETIC ANALYSIS OF BIOLOGICAL CLOCKS IN CELLS
    Carl Johnson; Fiscal Year: 2005
    ..and medical studies have shown that circadian rhythmicity is involved in depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia...
  33. BRET INTERACTION SYSTEM FOR CIRCADIAN AND OTHER PROTEINS
    Carl Johnson; Fiscal Year: 2001
    ..studies have shown that circadian rhythmicity is involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia...
  34. INPUT/OUTPUT ANALYSIS OF CELLULAR CIRCADIAN RHYTHMS
    Carl Johnson; Fiscal Year: 1992
    ..studies have shown that circadian rhythmicity is involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia...
  35. GLUTAMATERIC MECHANISMS OF DRUG-CONDITIONED BEHAVIOR
    Robert Balster; Fiscal Year: 2004
    ..stimulation, 3) the responding maintained by conditioned reinforcers using intravenous drug self-administration procedures; 4) conditioned components of drug tolerance and dependence; and 5) post-abstinent increase in drug consumption.
  36. PSYCHOPHARMACOLOGY IN BEHAVIORAL DENTISTRY AND MEDICINE
    Douglas Ramsay; Fiscal Year: 1999
    ..has theoretical importance to our understanding of the brain-behavioral systems underlying drug addiction and drug tolerance. His primary research interest is in the area of drugs and behavior...
  37. MOLECULAR MECHANISM OF ADENYLYL CYCLASE SUPERACTIVATION
    HENRY YAMAMURA; Fiscal Year: 2006
    ..Better understanding of the molecular mechanisms of drug tolerance at the human delta opioid receptor should aid in the development of longer acting analgesics with fewer side ..
  38. Receptor-G protein coupling in neurons
    MARIA DIVERSE; Fiscal Year: 2006
    ..useful in the treatment of disorders associated with elevated neurotransmitter levels, such as stroke, or clinical problems, such as drug tolerance, that are associated with unnaturally high extracellular hormone or drug concentrations.
  39. Receptor Structural Features Determining Drug Tolerance
    Spiro Pavlopoulos; Fiscal Year: 2006
    b>Drug tolerance is a key issue in understanding drug addiction and is of great importance in the treatment of chronic diseases...
  40. STRESS PROTEINS, DRUG TOLERANCE AND CELLULAR DEPRIVATION
    John Subjeck; Fiscal Year: 1992
    ....
  41. PSYCHOSTIMULANT REGULATION OF NEURAL GENE EXPRESSION
    Christine Konradi; Fiscal Year: 2003
    ..Repeated abuse of these drugs causes the long-term behavioral consequences of drug addiction, drug tolerance, and drug sensitization...
  42. MOLECULAR/GENETIC ANALYSIS OF BIOLOGICAL CLOCKS
    Carl Johnson; Fiscal Year: 2003
    ..studies have shown that these biological clocks are involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia...
  43. MOLECULAR PHYSIOLOGY OF OLFACTORY TRANSDUCTION
    Stuart Firestein; Fiscal Year: 2000
    ..The qualification of adaptation may help to understand such clinically crucial issues as drug tolerance and drug efficacy...
  44. Regulation of G-protein signaling in CNS neurons
    Nevin Lambert; Fiscal Year: 2006
    ..It is thought that desensitization underlies drug tolerance, whereas signals produced by receptors that do not desensitize may lead to the adaptive changes that underlie ..
  45. BRET Interaction System for Circadian Clock Proteins
    Carl Johnson; Fiscal Year: 2005
    ..studies have shown that circadian rhythmicity is involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, alertness, and insomnia...
  46. CIRCADIAN REGULATORY CIRCUITS IN DROSOPHILA
    Paul Hardin; Fiscal Year: 2003
    ..and well being since basic physiological activities including sleep, endocrine and cardiovascular function and drug tolerance are rhythmically controlled...
  47. Cell-permeant Clock Proteins
    Carl Johnson; Fiscal Year: 2003
    ..studies have shown that circadian rhythmicity is involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia...
  48. Behavioral Influences on Drug Tolerance
    James Smith; Fiscal Year: 2005
    ..Additionally, "multi-chamber" procedures will study generalization of those discriminative effects to performance of the same subjects in different circumstances. ..
  49. Targeting a reversibly drug tolerant cancer cell subpopulation
    Marie K Classon; Fiscal Year: 2010
    ..We will also consider potential roles for other cellular proteins or pathways in drug tolerance, making use of genomic and proteomic technologies to compare the expression and activation of proteins and ..
  50. Timing: Pharmacology and Conditioning
    Peter Balsam; Fiscal Year: 2005
    ..Furthermore, cues associated with drug-taking are important modulators of drug tolerance, craving and relapse...
  51. OPIOID TOLERANCE--ASSOCIATIVE AND NONASSOCIATIVE EFFECT
    Stephen Tiffany; Fiscal Year: 1999
    ..The results may have direct implications for the development of drug tolerance and dependence in addictive disorders...
  52. Chromatin Remodeling as a Mechanism to Produce Drug Tolerance
    Nigel Atkinson; Fiscal Year: 2009
    ..histone acetylation at this site to determine if it simultaneously blocks slowpoke induction and behavioral drug tolerance. Briefly, transposons carrying Gal4 UAS binding sites have been positioned within the slowpoke control region...
  53. Spatiotemporal Dynamics of Emotional Memory Networks
    KEVIN LABAR; Fiscal Year: 2005
    ..role in motivational aspects of the addictive process and contribute to physiological adaptations underlying drug tolerance. The proposed studies may lead to new insights into understanding these effects by providing a more accurate ..
  54. Circadian Regulation of Olfaction
    STUART DRYER; Fiscal Year: 2004
    ..and well being since basic physiological activities including sleep, endocrine and cardiovascular function and drug tolerance are rhythmically controlled...
  55. Molecular bases of addictive memories
    Cristina Alberini; Fiscal Year: 2004
    ..many compounds that impair memory formation and inhibit memory-associated molecular pathway also attenuate drug tolerance and dependence...
  56. Molecular Components Underlying Drug Abuse
    Charles Chavkin; Fiscal Year: 2006
    ..2) the Behavioral Core (Bernstein & External Advisors) would standardize the analysis of drug effects and drug tolerance; and 3) the Anatomy Core (Westenbroek) would perform a generalized neuroanatomical characterization and ..
  57. Transgene for morphine tolerance and withdrawal
    Shuanglin Hao; Fiscal Year: 2005
    ..Preventing the transition from drug use to drug tolerance/withdrawal has important clinical implications...
  58. MORRIS BROWN COLLEGE DRUG ABUSE RESEARCH DEVELOPMENT PROGRAM
    JEANNE STAHL; Fiscal Year: 2005
    ..To our existing cluster of animal research projects on drug tolerance and drug discrimination, we propose to add several human projects on drug abuse prevention and treatment...
  59. MU OPIOID RECEPTOR--PHOSPHORYLATION AND DESENSITIZATION
    Jia Bei Wang; Fiscal Year: 2002
    ..It should have an impact on our knowledge to the molecular mechanism of drug tolerance, dependence and addiction...
  60. Contribution of the PAG to morphine tolerance
    Michael Morgan; Fiscal Year: 2002
    ..In the long term, such knowledge should improve the treatment of pain by allowing therapies that disrupt tolerance to be developed. ..
  61. ACUTE TOLERANCE IN ANESTHETIC ACTIONS AND INTERACTIONS
    Igor Kissin; Fiscal Year: 2001
    ....
  62. Neural blockade with vanilloids
    Igor Kissin; Fiscal Year: 2007
    ..To study the specific aims of the project the effects of RTX will be examined in rats by behavioral methods; and whole cell voltage-clamp technique will be used to identify a mechanism for impulse failure induced by RTX. ..
  63. LEVEL OF RESPONSE TO ALCOHOL AND BRAIN FUNCTIONING
    Marc A Schuckit; Fiscal Year: 2010
    ..The project will also expand our understanding of the neural substrates of the level of response to alcohol, a key risk factor for the development of alcohol dependence. ..
  64. Prospective Study: Alcoholic & Control Family Offspring
    Marc A Schuckit; Fiscal Year: 2010
    ..Our ultimate goal is to identify ways to prevent the escalation of drinking and associated problems in young populations. ..