Research Topics
| Richard OlsenSummaryAffiliation: University of California Country: USA Publications
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Publications
Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptorsElisabetta Cagetti
Department of Molecular and Medical Pharmacology, School of Medicine, University of California Los Angeles, Los Angeles, California 90095 1735, USA
Mol Pharmacol 63:53-64. 2003..These data suggest that specific alterations in GABAR occur after CIE and may underlie the development of hyperexcitability and ethanol dependence...
GABA A receptors: subtypes provide diversity of function and pharmacologyRichard W Olsen
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1735, USA
Neuropharmacology 56:141-8. 2009..This list was first presented by Olsen & Sieghart (in press)...- Picrotoxin-like channel blockers of GABAA receptorsRichard W Olsen
Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California, Los Angeles, CA 90095-1735, USA
Proc Natl Acad Sci U S A 103:6081-2. 2006 - Plasticity of GABAA receptors in brains of rats treated with chronic intermittent ethanolRichard W Olsen
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
Neurochem Res 30:1579-88. 2005.... - GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulationRichard W Olsen
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
Can J Anaesth 58:206-15. 2011..The purpose of this review is to summarize current knowledge of detailed biochemical evidence for the role of γ-aminobutyric acid type A receptors (GABA(A)-Rs) in the mechanisms of general anesthesia... - Fishing for allosteric sites on GABA(A) receptorsRichard W Olsen
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
Biochem Pharmacol 68:1675-84. 2004..It is likely that concrete structural information will be forthcoming soon... - International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. UpdateRichard W Olsen
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
Pharmacol Rev 60:243-60. 2008..The list is divided into three categories of native receptor subtypes: "identified," "existence with high probability," and "tentative.".. - GABAA receptor subtypes: the "one glass of wine" receptorsRichard W Olsen
Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California, Los Angeles, Room 23 120 CHS, 650 Charles E Young Drive South, Los Angeles, CA 90095 1735, USA
Alcohol 41:201-9. 2007..However, many important open questions remain to be answered... - Functional consequences of GABAA receptor alpha 4 subunit deletion on synaptic and extrasynaptic currents in mouse dentate granule cellsJing Liang
Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, California 90095 1668, USA
Alcohol Clin Exp Res 32:19-26. 2008.... - Identification of the bovine gamma-aminobutyric acid type A receptor alpha subunit residues photolabeled by the imidazobenzodiazepine [3H]Ro15-4513Gregory W Sawyer
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA
J Biol Chem 277:50036-45. 2002..These results are discussed in terms of a homology model of the benzodiazepine-binding site based on the molluscan acetylcholine-binding protein structure... - A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activationChang Sheng S Chang
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095 1735, USA
J Biol Chem 278:42821-8. 2003.... - Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependenceJing Liang
Division of Oral Biology and Medicine, School of Dentistry, UCLA, Los Angeles, CA 90095-1668, USA
J Pharmacol Exp Ther 310:1234-45. 2004.... - Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activityH Jacob Hanchar
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
Nat Neurosci 8:339-45. 2005..These findings identify extrasynaptic GABARs as critical targets underlying low-dose alcohol intoxication and demonstrate that subtle changes in tonic inhibition in one class of neurons can alter behavior... - Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptorsH Jacob Hanchar
Department of Molecular and Medical Pharmacology, University of California-Los Angeles, Charles Young Drive South, Los Angeles, CA 90095, USA
Proc Natl Acad Sci U S A 103:8546-51. 2006.... - Alcohol- and alcohol antagonist-sensitive human GABAA receptors: tracking δ subunit incorporation into functional receptorsPratap Meera
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 1735, USA
Mol Pharmacol 78:918-24. 2010..These data are consistent with the notion that δ subunit-incorporation is often incomplete in recombinant systems yet is necessary for high ethanol sensitivity, one of the features of native δ subunit-containing GABA(A)Rs... - Contributions of the GABAA receptor alpha6 subunit to phasic and tonic inhibition revealed by a naturally occurring polymorphism in the alpha6 geneVijayalakshmi Santhakumar
Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
J Neurosci 26:3357-64. 2006.... - Tolerance to sedative/hypnotic actions of GABAergic drugs correlates with tolerance to potentiation of extrasynaptic tonic currents of alcohol-dependent ratsJing Liang
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room CHS 23 120, 650 Young Drive South, Los Angeles, CA 90095 1735, USA
J Neurophysiol 102:224-33. 2009..This requires the reasonable assumption that the same types of GABAARs in other brain regions involved directly in hypnotic drug actions show similar tolerance... - GABA(A) receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrainZechun Peng
Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095 1763, USA
J Comp Neurol 446:179-97. 2002..This suggests that the additional subunit changes are directly linked to loss of the delta subunit and could reflect local changes in subunit composition and function of GABA(A) receptors in delta-/- mice... - Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptorsJing Liang
Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California 90095, USA
J Neurosci 26:1749-58. 2006.... - Numerous classes of general anesthetics inhibit etomidate binding to gamma-aminobutyric acid type A (GABAA) receptorsGuo dong Li
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA
J Biol Chem 285:8615-20. 2010.... - Behavior and physiology of mice lacking the GABAA-receptor delta subunitIgor Spigelman
Division of Oral Biology and Medicine, UCLA School of Dentistry, 10833 Le Conte Avenue, 63 050 CHS, Los Angeles, CA 90095 1668, USA
Epilepsia 43:3-8. 2002..This study further characterized the behavior and physiology of the delta mutants... - Long-term effects of diazepam treatment of epileptic GABAA receptor beta3 subunit knockout mouse in early lifePatricia Liljelund
Brain Research Institute, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA
Epilepsy Res 66:99-115. 2005.... - GABAA receptor beta3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta3 subunit levels, EEG, and behaviorPatricia Liljelund
Brain Research Institute and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA
Brain Res Dev Brain Res 157:150-61. 2005.... - Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analogGuo-Dong Li
Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
J Neurosci 26:11599-605. 2006.... - GABAA receptor-associated protein traffics GABAA receptors to the plasma membrane in neuronsTarek A Leil
Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095 1735
J Neurosci 24:11429-38. 2004.... - Neurosteroids allosterically modulate binding of the anesthetic etomidate to gamma-aminobutyric acid type A receptorsGuo dong Li
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
J Biol Chem 284:11771-5. 2009..M., Wilkins, M. E., da Silva, H. M., and Smart, T. G. (2006) Nature 444, 486-489) are located at the subunit interface defined by our etomidate site model... - Reduced inhibition and sensitivity to neurosteroids in hippocampus of mice lacking the GABA(A) receptor delta subunitIgor Spigelman
Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, California 90095 1668, USA
J Neurophysiol 90:903-10. 2003.... - Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant alpha4beta3delta and alpha4beta3 GABA A receptors expressed in HEK cellsPratap Meera
Department of Neurobiology, Geffen School of Medicine, University of California, Los Angeles, USA
Neuropharmacology 56:155-60. 2009..Increasing GABA efficacy on alpha4/6beta3delta and alpha4beta3 receptors is likely to make an important contribution to the anesthetic effects of etomidate, propofol and the neurosteroid THDOC... - Low dose acute alcohol effects on GABA A receptor subtypesMartin Wallner
Department of Molecular and Medical Pharmacology, Geffen School of Medicine at UCLA, Room 23-120 CHS, 650 Charles Young Drive South, Los Angeles, CA 90095-1735, USA
Pharmacol Ther 112:513-28. 2006..We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABA(A)R subtypes... - Chronic intermittent ethanol (CIE) administration in rats decreases levels of neurosteroids in hippocampus, accompanied by altered behavioral responses to neurosteroids and memory functionElisabetta Cagetti
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, University of California, Room CHS 23-120, 650 Young Drive South, Los Angeles, CA 90095-1735, USA
Neuropharmacology 46:570-9. 2004..These results suggest that changes in neurosteroids level and in vivo sensitivity to these compounds are involved in the development of ethanol dependence in the CIE model... - Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptorsJesper Nymann-Andersen
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California, USA
J Neurochem 80:815-23. 2002.... - Interaction between GABAA receptor subunit intracellular loops: implications for higher order complex formationJesper Nymann-Andersen
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1735, USA
J Neurochem 83:1164-71. 2002..We propose a model for GABAA receptor clustering based on GABARAP and GABAA receptor subunit-subunit interaction... - Mechanisms of reversible GABAA receptor plasticity after ethanol intoxicationJing Liang
Division of Oral Biology and Medicine, School of Dentistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
J Neurosci 27:12367-77. 2007..This leads to transcriptionally regulated increases in alpha4 and gamma2 and decreases in alpha1 subunits, with preferential insertion of the newly formed alpha4betagamma2 GABA(A)Rs at synapses... - Biochemical identification of the binding domain in the GABA(A) receptor-associated protein (GABARAP) mediating dimer formationJesper Nymann-Andersen
Department of Molecular and Medical Pharmacology, CHS 23 120, UCLA School of Medicine, Los Angeles, CA 90095 1735, USA
Neuropharmacology 43:476-81. 2002..The identification of binding domains in GABARAP allows for the study of GABARAP functions, including GABA(A) receptor dynamics... - Topiramate attenuates withdrawal signs after chronic intermittent ethanol in ratsElisabetta Cagetti
Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Room CHS 23-120, 650 Young Drive South, Los Angeles, CA 90095, USA
Neuroreport 15:207-10. 2004..On the elevated plus-maze, Topiramate was markedly more effective in CIE rats than in controls. Topiramate may have a therapeutic efficacy in treating alcohol withdrawal symptoms... - Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer?H Jacob Hanchar
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Room 23 338 CHS, 650 Charles Young Drive South, Los Angeles, CA 90095 1735, USA
Life Sci 76:1-8. 2004..Receptors containing the delta subunit are thought to be located extrasynaptically and it will be important to determine if these extrasynaptic GABA(A) receptor subunit combinations mediate low dose alcohol effects in vivo... - GABAA receptor associated proteins: a key factor regulating GABAA receptor functionZi Wei Chen
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California, 90095 1735, USA
J Neurochem 100:279-94. 2007..This article reviews the current studies of GABA(A) receptor intracellular loop-associated proteins... - Pharmacologic evidence for abnormal thalamocortical functioning in GABA receptor beta3 subunit-deficient mice, a model of Angelman syndromeAdrian Handforth
Department of Neurology, VA Greater Los Angeles Health Care System, Los Angeles, CA 90073, USA
Epilepsia 46:1860-70. 2005.... - Plasticity of GABAA receptors after ethanol pre-exposure in cultured hippocampal neuronsYi Shen
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 1735, USA
Mol Pharmacol 79:432-42. 2011.... - C-terminal modification is required for GABARAP-mediated GABA(A) receptor traffickingZi Wei Chen
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095 1735, USA
J Neurosci 27:6655-63. 2007..These results suggest that glycine 116 is required for C-terminal processing of GABARAP and that processing is essential for the localization of GABARAP and its functions as a trafficking protein... - GABAA receptor-associated protein regulates GABAA receptor cell-surface number in Xenopus laevis oocytesZi Wei Chen
Department of Molecular and Medical Pharmacology, Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095 1735, USA
Mol Pharmacol 68:152-9. 2005..Rather, it seems to supplement inadequate amounts of endogenous GABARAP to support optimum trafficking and/or stabilization of surface GABA(A) receptors... - Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsyMiyabi Tanaka
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA
Am J Hum Genet 82:1249-61. 2008.... - 2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: a derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channelsS Shaukat Husain
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
J Med Chem 46:1257-65. 2003..The latter increase was confined to a proteolytic fragment containing the first three transmembrane segments. Thus, R-(+)-azietomidate is a potent stereoselective general anesthetic and an effective photolabel... - Point mutation in the first transmembrane region of the beta 2 subunit of the gamma--aminobutyric acid type A receptor alters desensitization kinetics of gamma--aminobutyric acid- and anesthetic-induced channel gatingA Christine Engblom
Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen 2100, Denmark
J Biol Chem 277:17438-47. 2002..01). The present findings suggest that this TM1 glycine residue is critical for the rate at which desensitization occurs and that both GABA and intravenous anesthetics implement an analogous pathway for generating desensitization... - Conductance of recombinant GABA (A) channels is increased in cells co-expressing GABA(A) receptor-associated proteinAndrea B Everitt
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia
J Biol Chem 279:21701-6. 2004..quot; Recombinant channels may require the influence of GABARAP and perhaps other intracellular proteins to adopt a fuller repertoire of properties of native channels... - Normal acute behavioral responses to moderate/high dose ethanol in GABAA receptor alpha 4 subunit knockout miceDev Chandra
Departments of Anesthesiology and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
Alcohol Clin Exp Res 32:10-8. 2008..We therefore hypothesized that those behavioral responses to EtOH that are mediated by alpha 4-containing GABA(A)-Rs would be diminished in alpha 4 knockout mice... - Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channelsS Shaukat Husain
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114 USA
J Med Chem 49:4818-25. 2006..Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia... - GABA(A)-R alpha1 subunit knockin mutation leads to abnormal EEG and anesthetic-induced seizure-like activity in miceFrank P Elsen
Department of Anesthesiology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
Brain Res 1078:60-70. 2006.... - Six decades of GABANorman Bowery
Biochem Pharmacol 68:1477-8. 2004
Research Grants
- GABA-A RECEPTOR STRUCTURE & FUNCTIONRichard Olsen; Fiscal Year: 1993..The information gained will be valuable in the understanding of normal and diseased brain function. Human disorders of particular relevance include epilepsy, anxiety, alcohol dependence, and sleep disorders...
- GABA(A) Receptor Complex In Alcohol DependenceRichard W Olsen; Fiscal Year: 2010..The amounts, locations, and functions of the GABA receptors are related to the behavioral changes seen in alcohol dependence such as hyperexcitability, increased anxiety, sleep disturbances, and seizure susceptibility. ..
- GABA-A RECEPTOR STRUCTURE AND FUNCTIONRichard Olsen; Fiscal Year: 2003..Studies on these and related proteins will allow us to take a close look a dynamic and important cellular biology of these important brain neurotransmitter receptors. ..
- GABA(A) Receptor Complex In Alcohol DependenceRichard Olsen; Fiscal Year: 2009..The amounts, locations, and functions of the GABA receptors are related to the behavioral changes seen in alcohol dependence such as hyperexcitability, increased anxiety, sleep disturbances, and seizure susceptibility. ..
- GABA RECEPTOR COMPLEX IN ALCOHOL DEPENDENCERichard Olsen; Fiscal Year: 1990....
- GABA(A) Receptor Complex In Alcohol DependenceRichard Olsen; Fiscal Year: 2009..The amounts, locations, and functions of the GABA receptors are related to the behavioral changes seen in alcohol dependence such as hyperexcitability, increased anxiety, sleep disturbances, and seizure susceptibility. ..