gaba b receptors

Summary

Summary: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and influence cells via interactions with G-proteins. GABA-B receptors are pharmacologically characterized by their insensitivity to the blocker bicuculline and sensitivity to the agonist L-baclofen. They are found both presynaptically and postsynaptically, and act variously by inhibition of adenylate cyclase, activation of phospholipase A2, activation of potassium channels, and inactivation of voltage-activated calcium channels.

Top Publications

  1. ncbi Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy
    H C Peters
    Molecular Human Genetics, Ruhr University, D 44780 Bochum, Germany
    Neurogenetics 2:47-54. 1998
  2. ncbi Comparison of receptive field expansion produced by GABA(B) and GABA(A) receptor antagonists in raccoon primary somatosensory cortex
    S A Chowdhury
    Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
    Exp Brain Res 144:114-21. 2002
  3. ncbi Molecular structure and physiological functions of GABA(B) receptors
    Bernhard Bettler
    Pharmazentrum, Dept of Clinical Biological Sciences, Institute of Physiology, Univ of Basel, Klingelbergstr 50, CH 4056 Basel, Switzerland
    Physiol Rev 84:835-67. 2004
  4. ncbi C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors
    A Pagano
    Novartis Pharma AG, Therapeutic Area Nervous System, CH-4002 Basle, Switzerland
    J Neurosci 21:1189-202. 2001
  5. pmc The availability of surface GABA B receptors is independent of gamma-aminobutyric acid but controlled by glutamate in central neurons
    Karina J Vargas
    Fisiologia y Biofisica, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
    J Biol Chem 283:24641-8. 2008
  6. ncbi GABA(B) receptors: synaptic functions and mechanisms of diversity
    Daniel Ulrich
    Pharmazentrum, Institute of Physiology, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Curr Opin Neurobiol 17:298-303. 2007
  7. ncbi International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function
    N G Bowery
    Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, United Kingdom
    Pharmacol Rev 54:247-64. 2002
  8. ncbi Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition
    Hamdy Shaban
    Friedrich Miescher Institute for Biomedical Research, CH 4058 Basel, Switzerland
    Nat Neurosci 9:1028-35. 2006
  9. ncbi SGS742: the first GABA(B) receptor antagonist in clinical trials
    Wolfgang Froestl
    Neuroscience Research, Novartis Pharma AG, WKL 136 5 25, CH 4002 Basel, Switzerland
    Biochem Pharmacol 68:1479-87. 2004
  10. ncbi Functional expression of metabotropic GABAB receptors in primary cultures of astrocytes from rat cerebral cortex
    Michiko Oka
    Department of Biochemical Pharmacology, Kyoto Pharmaceutical University, Misasagi, Kyoto, Japan
    Biochem Biophys Res Commun 341:874-81. 2006

Detail Information

Publications242 found, 100 shown here

  1. ncbi Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy
    H C Peters
    Molecular Human Genetics, Ruhr University, D 44780 Bochum, Germany
    Neurogenetics 2:47-54. 1998
    ..However, clinically unaffected relatives did carry the same variations, excluding these amino acid substitutions as the cause for IGE in these families...
  2. ncbi Comparison of receptive field expansion produced by GABA(B) and GABA(A) receptor antagonists in raccoon primary somatosensory cortex
    S A Chowdhury
    Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7
    Exp Brain Res 144:114-21. 2002
    ..These results indicate that both GABA(B) and GABA(A) receptors play a role in shaping the normal receptive fields in somatosensory cortex...
  3. ncbi Molecular structure and physiological functions of GABA(B) receptors
    Bernhard Bettler
    Pharmazentrum, Dept of Clinical Biological Sciences, Institute of Physiology, Univ of Basel, Klingelbergstr 50, CH 4056 Basel, Switzerland
    Physiol Rev 84:835-67. 2004
    ..Here we review current concepts on the molecular composition and function of GABA(B) receptors and discuss ongoing drug-discovery efforts...
  4. ncbi C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors
    A Pagano
    Novartis Pharma AG, Therapeutic Area Nervous System, CH-4002 Basle, Switzerland
    J Neurosci 21:1189-202. 2001
    ..Rather than guaranteeing heterodimerization, as previously assumed, the coiled-coil structure appears to be important for export of the receptor complex from the secretory apparatus...
  5. pmc The availability of surface GABA B receptors is independent of gamma-aminobutyric acid but controlled by glutamate in central neurons
    Karina J Vargas
    Fisiologia y Biofisica, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
    J Biol Chem 283:24641-8. 2008
    ..These observations indicate that glutamate and not GABA controls the abundance of surface GABA(B) receptors in central neurons, consistent with their enrichment at glutamatergic synapses...
  6. ncbi GABA(B) receptors: synaptic functions and mechanisms of diversity
    Daniel Ulrich
    Pharmazentrum, Institute of Physiology, University of Basel, Klingelbergstrasse 50 70, CH 4056 Basel, Switzerland
    Curr Opin Neurobiol 17:298-303. 2007
    ..Finally, we provide possible explanations for the perplexing situation that GABA(B) receptor subtypes that have indistinguishable properties in vitro generate distinct GABA(B) responses in vivo...
  7. ncbi International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function
    N G Bowery
    Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, United Kingdom
    Pharmacol Rev 54:247-64. 2002
    ..The advent of GABA(B1) knockout mice has also failed to provide support for multiple receptor types...
  8. ncbi Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition
    Hamdy Shaban
    Friedrich Miescher Institute for Biomedical Research, CH 4058 Basel, Switzerland
    Nat Neurosci 9:1028-35. 2006
    ....
  9. ncbi SGS742: the first GABA(B) receptor antagonist in clinical trials
    Wolfgang Froestl
    Neuroscience Research, Novartis Pharma AG, WKL 136 5 25, CH 4002 Basel, Switzerland
    Biochem Pharmacol 68:1479-87. 2004
    ..A second Phase II clinical trial in 280 Alzheimer's disease patients is underway...
  10. ncbi Functional expression of metabotropic GABAB receptors in primary cultures of astrocytes from rat cerebral cortex
    Michiko Oka
    Department of Biochemical Pharmacology, Kyoto Pharmaceutical University, Misasagi, Kyoto, Japan
    Biochem Biophys Res Commun 341:874-81. 2006
    ..Taken collectively, these results demonstrate that functionally active metabotropic GABA(B) receptors are expressed in rat cerebrocortical astrocytes...
  11. ncbi GABA(B)-receptor subtypes assemble into functional heteromeric complexes
    K Kaupmann
    Novartis Pharma AG, TA Nervous System, Basel, Switzerland
    Nature 396:683-7. 1998
    ..Heteromeric assembly among G-protein-coupled receptors has not, to our knowledge, been described before...
  12. ncbi GABA induces terminal differentiation of Dictyostelium through a GABAB receptor
    Christophe Anjard
    Center for Molecular Genetics, Division of Biological Sciences, University of California San Diego, La Jolla, 92093 0368, USA
    Development 133:2253-61. 2006
    ..These results indicate that GABA is not only a neurotransmitter but also an ancient intercellular signal...
  13. pmc Selective gating of glutamatergic inputs to excitatory neurons of amygdala by presynaptic GABAb receptor
    Bing Xing Pan
    Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892, USA
    Neuron 61:917-29. 2009
    ..Thus, target-cell-specific control of glutamate release by presynaptic GABAbR orchestrates the inhibitory dominance inside amygdala and might contribute to prevention of nonadaptive defensive behaviors...
  14. ncbi Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice
    Martin Gassmann
    Pharmazentrum, Department of Clinical Biological Sciences, University of Basel, CH 4056 Basel, Switzerland
    J Neurosci 24:6086-97. 2004
    ..It is therefore possible that functional GABAB receptors exist in neurons that naturally lack GABAB(2) subunits...
  15. ncbi Gap-junctional coupling between neurogliaform cells and various interneuron types in the neocortex
    Anna Simon
    Department of Comparative Physiology, University of Szeged, Szeged H 6726, Hungary
    J Neurosci 25:6278-85. 2005
    ..Widespread electrical connections might enable neurogliaform cells to monitor the activity of different interneurons acting on GABA(A) receptors at various regions of target cells...
  16. ncbi Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1))
    V Schuler
    Novartis Pharma AG, TA Nervous System, CH 4002, Basel, Switzerland
    Neuron 31:47-58. 2001
    ..This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes...
  17. ncbi GABA spillover activates postsynaptic GABA(B) receptors to control rhythmic hippocampal activity
    M Scanziani
    Brain Research Institute, University of Zurich, Switzerland
    Neuron 25:673-81. 2000
    ..Thus, activation of extrasynaptic GABA(B)Rs by pooling of GABA is an important mechanism regulating hippocampal network activity...
  18. ncbi Effect of GABA(B) receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon
    Jyoti N Sengupta
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Gastrointest Liver Physiol 283:G1343-51. 2002
    ..Results suggest a peripheral role of GABA(B) receptors in the inhibition of mechanotransduction property of distension-sensitive pelvic nerve afferent fibers...
  19. ncbi Heterodimerization is required for the formation of a functional GABA(B) receptor
    J H White
    Receptor Systems, Molecular Pharmacology Unit, GlaxoWellcome, Medicines Research Centre, Stevenage, Hertfordshire, UK
    Nature 396:679-82. 1998
    ..These results indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers composed of GABA(B)R1 and GABA(B)R2...
  20. pmc GABA(B) receptor modulation of feedforward inhibition through hippocampal neurogliaform cells
    Christopher J Price
    Medical Research Council Anatomical Neuropharmacology Unit, Oxford OX1 3TH, United Kingdom
    J Neurosci 28:6974-82. 2008
    ..The NGFC-CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells...
  21. pmc Phospho-dependent functional modulation of GABA(B) receptors by the metabolic sensor AMP-dependent protein kinase
    Nobuyuki Kuramoto
    Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuron 53:233-47. 2007
    ..Together our results provide evidence of a neuroprotective mechanism, which, under conditions of metabolic stress or after ischemia, increases GABA(B) receptor function to reduce excitotoxicity and thereby promotes neuronal survival...
  22. ncbi Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) and GABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion
    K J Charles
    Neurology CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK
    Neuroscience 106:447-67. 2001
    ..Overall our data suggest that GABA(B) receptors are widely expressed throughout the brain and spinal cord, and that GABA(B1a) and GABA(B1b) subunits can associate with GABA(B2) to form both pre- and post-synaptic receptors...
  23. ncbi GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization
    J M Fritschy
    Institute of Pharmacology, Swiss Federal Institute of Technology ETH, University of Zurich, Switzerland
    Eur J Neurosci 11:761-8. 1999
    ..This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand...
  24. pmc Syntheses and optimization of new GS39783 analogues as positive allosteric modulators of GABA B receptors
    Sebastien Guery
    Novartis Institutes for BioMedical Research, Neuroscience, Novartis Pharma A G, Basel, Switzerland
    Bioorg Med Chem Lett 17:6206-11. 2007
    ..The optimization of GS39783 into potent, selective, and safe positive allosteric modulators of GABA(B) receptors is presented...
  25. ncbi Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex of the rat
    Peter T Ohara
    Departments of Anatomy and the W M Keck Foundation Center for Integrative Neuroscience, University of California San Francisco, San Francisco, CA 94143, USA
    J Neurocytol 32:131-41. 2003
    ..Through these connections, dopamine innervation of the RAIC is likely to affect the motivational and affective dimensions of pain...
  26. ncbi Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor cell surface stability
    Benjamin P Fairfax
    Medical Research Council Laboratory of Molecular Cell Biology and Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
    J Biol Chem 279:12565-73. 2004
    ..We propose that signaling pathways that regulate cAMP levels in neurons may have profound effects on the tonic synaptic inhibition by modulating the availability of GABA(B) receptors...
  27. ncbi The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses
    Nicole Guetg
    Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, 4056 Basel, Switzerland
    J Neurosci 29:1414-23. 2009
    ..This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance...
  28. ncbi Activaton of GABAB receptor inhibits the excitability of rat small diameter trigeminal root ganglion neurons
    M Takeda
    Department of Physiology, School of Dentistry at Tokyo, Nippon Dental University, 1 9 20, Fujimi cho, Chiyoda ku, Tokyo, 102 8159, Japan
    Neuroscience 123:491-505. 2004
    ....
  29. ncbi [History and the present of metabotropic GABAB receptor]
    M Franek
    Univerzita Karlova, 3 lékarská fakulta, Ustav normální patologické a klinické fyziologie, Praha
    Cesk Fysiol 53:117-24. 2004
    ..Recently, a novel GPCR with close relation to GABAB was cloned. It was termed GABABL, its role in GABAB activation has not been discovered yet...
  30. ncbi Distribution and depression of the GABA(B) receptor in the spinal dorsal horn of adult rat
    K Yang
    Department of Anatomy and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an, People's Republic of China
    Brain Res Bull 55:479-85. 2001
    ....
  31. ncbi Floxed allele for conditional inactivation of the GABAB(1) gene
    Corinne Haller
    Pharmazentrum, University of Basel, Department of Clinical Biological Sciences, Institute of Physiology, CH 4056 Basel, Switzerland
    Genesis 40:125-30. 2004
    ..The conditional GABA(B(1)) allele described here is therefore suitable for generating mice with a site- and time-specific loss of GABA(B) function...
  32. pmc Altered synaptic input and GABAB receptor function in spinal superficial dorsal horn neurons in rats with diabetic neuropathy
    Xiu Li Wang
    Department of Anaesthesiology and Pain Medicine, Unit 409, The University of Texas M D Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX 77030, USA
    J Physiol 579:849-61. 2007
    ..Furthermore, the function of presynaptic GABAB receptors at primary afferent terminals, but not that on GABAergic and glycinergic interneurons, in the spinal cord is reduced in diabetic neuropathy...
  33. ncbi GABA(B) receptor agonists for the treatment of drug addiction: a review of recent findings
    Michael S Cousins
    Department of Psychiatry, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Drug Alcohol Depend 65:209-20. 2002
    ..This line of research may also improve our understanding of the neurochemical mechanisms underlying the drug dependence process...
  34. ncbi Identification of two further splice variants of GABABR1 characterizes the conserved micro-exon 4 as a hot spot for regulated splicing in the rat brain
    Jethro Holter
    School of Biosciences, Cardiff University, Cardiff, UK
    J Mol Neurosci 26:99-108. 2005
    ..Conservation of GABABR1 micro-exon 4 across species suggests a conserved functional role, facilitating either N-terminal protein production or post-transcriptional gene regulation through regulated splicing coupled to transcript decay...
  35. pmc Local protein synthesis and GABAB receptors regulate the reversibility of long-term potentiation at murine hippocampal mossy fibre-CA3 synapses
    Chiung Chun Huang
    Department of Pharmacology, College of Medicine, National Cheng Kung University, No 1, Ta Hsiue Road, Tainan 701, Taiwan
    J Physiol 561:91-108. 2004
    ..These two factors may crucially regulate the reversal and stability of long-term information storage...
  36. ncbi Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded
    Stanislas Blein
    Edinburgh Protein Interaction Centre, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, Scotland, United Kingdom
    J Biol Chem 279:48292-306. 2004
    ..Thus, we have shown that the two CCP modules of GABA(B) R1a have strikingly different structural properties, reflecting their different functions...
  37. pmc Single- and multilocus allelic variants within the GABA(B) receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence
    Joke Beuten
    Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    Am J Hum Genet 76:859-64. 2005
    ..In summary, our findings provide evidence of a significant association of GABAB2 variants with ND, implying that this gene plays an important role in the etiology of this drug addiction...
  38. ncbi Nociceptive spinal neurons expressing NK1 and GABAB receptors are located in lamina I
    Ana Rita Castro
    Instituto de Histologia e Embriologia, Faculdade de Medicina e IBMC, Universidade do Porto, 4200 319 Porto, Portugal
    Brain Res 1003:77-85. 2004
    ....
  39. ncbi The Dictyostelium repertoire of seven transmembrane domain receptors
    Yogikala Prabhu
    Centre for Biochemistry, Medical Faculty, University of Cologne, Joseph Stelzmann Str 52, D 50931 Köln, Germany
    Eur J Cell Biol 85:937-46. 2006
    ..discoideum was surprising because they had not been observed outside the animal kingdom before. Their presence suggests unprecedentedly complex and so far unknown signaling activities in this lower eukaryote...
  40. pmc GABA B receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons
    Saobo Lei
    Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA
    J Physiol 546:439-53. 2003
    ....
  41. pmc Differential compartmentalization and distinct functions of GABAB receptor variants
    Rejan Vigot
    Department of Clinical Biological Sciences, Institute of Physiology, Pharmazentrum, University of Basel, CH 4056 Basel, Switzerland
    Neuron 50:589-601. 2006
    ..The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions...
  42. ncbi Secondary hyperalgesia in the monoarthritic rat is mediated by GABAB and NK1 receptors of spinal dorsal horn neurons: a behavior and c-fos study
    A R Castro
    Institute of Histology and Embryology, Faculdade de Medicina, Universidade do Porto, 4200 319 Porto, Portugal
    Neuroscience 141:2087-95. 2006
    ....
  43. ncbi Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice
    Klemens Kaupmann
    Novartis Institutes for BioMedical Research, WKL 125 7 42, Novartis Pharma AG, CH 4002 Basel, Switzerland
    Eur J Neurosci 18:2722-30. 2003
    ..It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB-binding sites remain elusive...
  44. ncbi No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits
    Julie Kniazeff
    Centre National de la Recherche Scientifique Unité Propre de Recherche 9023, Mecanismes Moleculaires des Communications Cellulaires, 34094 Montpellier Cedex 5, France
    J Neurosci 22:7352-61. 2002
    ..This suggests that the GB2 VFTM does not constitute a binding site for a natural ligand...
  45. ncbi Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor
    D A Schwarz
    Neurocrine Biosciences, Inc, San Diego, California 92121 1102, USA
    J Biol Chem 275:32174-81. 2000
    ..Despite this strong interaction, GABA(B(1e)) fails to disrupt G-protein coupled inwardly rectifying potassium activation by the full-length heterodimer pair of GABA(B(1a))/GABA(B(2))...
  46. ncbi GABA B receptor-mediated effects on expression of c-Fos in rat trigeminal nucleus following high- and low-intensity afferent stimulation
    M Takemura
    Department of Oral Anatomy, Osaka University Graduate School of Dentistry, 1 8 Yamadaoka, Suita, 565 0871, Osaka, Japan
    Neuroscience 103:1051-8. 2001
    ..Systemic administration of phaclofen could enhance nociceptive sensory activity but not non-nociceptive activity...
  47. ncbi The expression of GABA(B1) and GABA(B2) receptor subunits in the cNS differs from that in peripheral tissues
    A R Calver
    Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK
    Neuroscience 100:155-70. 2000
    ..Such areas are of interest as they may well contain novel GABA(B) receptor subunit isoforms, expression of which would enable the GABA(B1) subunit to reach the cell surface and form functional GABA(B) receptors...
  48. ncbi GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2
    K A Jones
    Synaptic Pharmaceutical Corporation, Paramus, New Jersey 07652, USA
    Nature 396:674-9. 1998
    ..We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors...
  49. ncbi Multiple functions of GABA A and GABA B receptors during pattern processing in the zebrafish olfactory bulb
    Rico Tabor
    Max Planck Institute for Medical Research, Heidelberg, Germany
    Eur J Neurosci 28:117-27. 2008
    ..GABA(A) and GABA(B) receptors are therefore differentially involved in multiple functions of neuronal circuits in the OB...
  50. ncbi The C-terminal domains of the GABA(b) receptor subunits mediate intracellular trafficking but are not required for receptor signaling
    A R Calver
    Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex CM19 5AW, United Kingdom
    J Neurosci 21:1203-10. 2001
    ..Furthermore although GABA(B1) is capable of producing GABA-binding sites, GABA(B2) is of central importance in the functional coupling of heteromeric GABA(B) receptors to G-proteins and the subsequent activation of effector systems...
  51. ncbi Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors
    K Kaupmann
    Novartis Pharma Inc, Research Department, Therapeutic Area Nervous System, Basel, Switzerland
    Nature 386:239-46. 1997
    ..The cloned receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate...
  52. ncbi GABA(B) receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord
    In Sun Choi
    Department of Pharmacology, School of Dentistry, Kyungpook National University, 188 1 Samduk 2 ga dong, Jung Gu, Daegu 700 412, Republic of Korea
    Pain 138:330-42. 2008
    ..Such GABA(B) receptor-mediated dynamic changes in short-term synaptic plasticity of glycinergic transmission onto SG neurons might contribute to the central processing of sensory signals...
  53. pmc Spinal nerve ligation does not alter the expression or function of GABA(B) receptors in spinal cord and dorsal root ganglia of the rat
    M P Engle
    Department of Pharmacology, The University of Iowa, Iowa City, IA 52242, USA
    Neuroscience 138:1277-87. 2006
    ....
  54. ncbi cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters
    Janine L Steiger
    Laboratory of Molecular Neurobiology, Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Neurosci 24:6115-26. 2004
    ....
  55. ncbi Subcellular localization of metabotropic GABA(B) receptor subunits GABA(B1a/b) and GABA(B2) in the rat hippocampus
    Akos Kulik
    Department of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany
    J Neurosci 23:11026-35. 2003
    ....
  56. ncbi Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain
    S Bischoff
    Novartis Pharma AG, Nervous System, CH 4002 Basel, Switzerland
    J Comp Neurol 412:1-16. 1999
    ..Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented...
  57. ncbi GABA(B) receptor expression and cellular localization in gerbil hippocampus after transient global ischemia
    F Vollenweider
    Functional Neuroanatomy, Institute of Anatomy, Basel University, Pestalozzistrasse 20, CH 4056 Basel, Switzerland
    Neurosci Lett 395:118-23. 2006
    ....
  58. ncbi Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice
    H M Prosser
    Genetics Research, Safety Assessment, Laboratory Animal Sciences, Neurology Centre of Excellence for Drug Discovery, Psychiatry Centre of Excellence for Drug Discovery, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom
    Mol Cell Neurosci 17:1059-70. 2001
    ..These data suggest that GABA(B) receptor antagonists may be of benefit in the treatment of psychiatric and neurological disorders in which attentional processing is impaired...
  59. ncbi GABA(B) receptors as potential therapeutic targets
    Claire Marie Vacher
    Pharmazentrum, University of Basel, Department of Physiology, Klingelbergstr 50 70, CH 4056 Basel, Switzerland
    Curr Drug Targets CNS Neurol Disord 2:248-59. 2003
    ..Here we provide and update on the molecular composition, the physiology and the pharmacology of GABA(B) receptors and discuss to what extent our current knowledge influences ongoing and future drug discovery efforts...
  60. ncbi GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy
    A Gambardella
    Institute of Neurology, School of Medicine, Catanzaro, Italy
    Neurology 60:560-3. 2003
    ..Dysfunction of gamma-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE)...
  61. ncbi Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated C-terminus
    K Wei
    Division of Neurology, Hospital for Sick Children, Faculty of Medicine, University of Toronto, Ontario, Canada
    Brain Res Mol Brain Res 89:103-10. 2001
    ..In addition, studies of hippocampus in developing animals indicated that the expression of GABA(B)R1g is maximal at postnatal day four. GABA(B)R1g could be generated by alternative splicing of the GABA(B)R1 gene...
  62. ncbi Enhanced activity of GABA receptors inhibits glutamate release induced by focal cerebral ischemia in rat striatum
    Changhan Ouyang
    Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, PR China
    Neurosci Lett 420:174-8. 2007
    ....
  63. ncbi Role of heteromer formation in GABAB receptor function
    R Kuner
    BASF LYNX Bioscience AG, Department of Neuroscience, Im Neuenheimer Feld 515, D 69120 Heidelberg, Germany
    Science 283:74-7. 1999
    ..Thus, the interaction of these receptors appears to be crucial for important physiological effects of GABA and provides a mechanism in receptor signaling pathways that involve a heterotrimeric GTP-binding protein...
  64. ncbi Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse
    Takeshi Sakaba
    Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany
    Nature 424:775-8. 2003
    ....
  65. ncbi Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions
    Dongxiao Sun
    Section of Neurobiology, Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA 22911, USA
    Neuropsychopharmacology 32:110-6. 2007
    ....
  66. pmc Molecular mechanisms contributing to long-lasting synaptic plasticity at the temporoammonic-CA1 synapse
    Miguel Remondes
    Caltech HHMI, Division of Biology, Pasadena, California 91125, USA
    Learn Mem 10:247-52. 2003
    ..These findings indicate that the TA-CA1 synapses may rely on a refined modulation of inhibition to exhibit LTP...
  67. ncbi Altered peripheral myelination in mice lacking GABAB receptors
    Valerio Magnaghi
    Department of Endocrinology and Centre of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy
    Mol Cell Neurosci 37:599-609. 2008
    ..In summary, our findings implicate GABA(B) receptors in the PNS myelination process and raise the possibility that PNS alterations contribute to the sensory phenotypes of GABA(B1)-deficient mice...
  68. ncbi Spontaneous synaptic activity is primarily GABAergic in vestibular nucleus neurons of the chick embryo
    Mei Shao
    Department of Anatomy and Cell Biology and Neuroscience Program, George Washington University Medical Center, Washington DC 20037, USA
    J Neurophysiol 90:1182-92. 2003
    ....
  69. pmc GABA(B) receptor-mediated presynaptic inhibition has history-dependent effects on synaptic transmission during physiologically relevant spike trains
    Patricia Ohliger-Frerking
    Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon 97006, USA
    J Neurosci 23:4809-14. 2003
    ....
  70. ncbi GABA(B) receptor activation and limbic network ictogenesis
    Massimo Avoli
    Departments of Neurology and Neurosurgery, and of Physiology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4
    Neuropharmacology 46:43-51. 2004
    ....
  71. ncbi Lamina-specific differences in GABA(B) autoreceptor-mediated regulation of spontaneous GABA release in rat entorhinal cortex
    Sarah J Bailey
    Department of Physiology and MRC Synaptic Plasticity Centre, School of Medical Sciences, University of Bristol, University Walk, BS8 1TD, Bristol, UK
    Neuropharmacology 46:31-42. 2004
    ..This demonstrates that GABA(B) autoreceptors are tonically activated by synaptically released GABA in layer V, and this may partly explain the lower level of spontaneous GABA release in the deep layer...
  72. ncbi Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA(B) autoreceptors in layer III of the entorhinal cortex
    Tengis Gloveli
    Johannes Müller Institute of Physiology at the Charité, Humboldt University Berlin, Tucholskystr 2, 10117, Berlin, Germany
    Neurobiol Dis 13:203-12. 2003
    ..Thus, in kindled animals activation of the layer III-CA1 pathway is facilitated by an increased GABA(B) receptor-mediated autoinhibition leading to an enhanced activation of the monosynaptic EC-CA1 pathway...
  73. ncbi Hypertension alters GABA receptor-mediated inhibition of neurons in the nucleus of the solitary tract
    Lin Mei
    Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 7764, USA
    Am J Physiol Regul Integr Comp Physiol 285:R1276-86. 2003
    ..The alterations are dependent on the subtype of GABA receptor being activated and whether the neuron receives a mono- or polysynaptic baroreceptor afferent input...
  74. pmc GABAB receptor- and metabotropic glutamate receptor-dependent cooperative long-term potentiation of rat hippocampal GABAA synaptic transmission
    Christian Patenaude
    Centre de Recherche en Sciences Neurologiques et Département de Physiologie, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
    J Physiol 553:155-67. 2003
    ..GABAergic synapses may therefore contribute to functional synaptic plasticity in adult hippocampus...
  75. ncbi Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus
    Kate E Chandler
    Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
    J Neurosci 23:11382-91. 2003
    ..Failure of GABA(B) receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus...
  76. ncbi GABAB-receptor-mediated suppression of sympathetic outflow from the spinal cord of neonatal rats
    Yi Wen Cheng
    Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
    J Appl Physiol (1985) 99:1658-67. 2005
    ..Our results suggest that the activation of intraspinal GABA(B) receptors suppresses SND via a mixture of ion events that may link to a change in Ca2+ conductance...
  77. ncbi Synaptically released GABA activates both pre- and postsynaptic GABA(B) receptors in the rat globus pallidus
    Katsuyuki Kaneda
    Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, TN 38163, USA
    J Neurophysiol 94:1104-14. 2005
    ..Together, we infer that both pre- and postsynaptic GABA(B) receptors may play crucial roles in the control of GP neuronal activity...
  78. ncbi Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro
    Kun Chen
    Department of Biological Science and Technology, School of Life Sciences, Mailbox 426, Nanjing University, China
    Brain Res Bull 67:310-8. 2005
    ....
  79. ncbi Effect of a high-salt diet on gamma-aminobutyric acid-mediated responses in the nucleus tractus solitarius of Sprague-Dawley rats
    Yuichi Masubuchi
    Second Department of Internal Medicine, Nihon University School of Medicine, 30 1, Oyaguchi Kamichou, Itabashi ku, Tokyo 173 8610, Japan
    Brain Res Bull 64:221-6. 2004
    ..Baroreflex sensitivity was similar. Thus, high-salt intake enhances both GABA(A) receptor- and GABA(B) receptor-mediated responses within NTS, thereby inhibiting elevation of AP...
  80. ncbi Induction of wakefulness and inhibition of active (REM) sleep by GABAergic processes in the nucleus pontis oralis
    M C Xi
    Department of Physiology, Brain Research Institute, School of Medicine, University of California, Los Angeles, CA 90095, USA
    Arch Ital Biol 139:125-45. 2001
    ..These data indicate that pontine GABAergic processes acting on both GABAA and GABAB receptors play a critical role in generating and maintaining wakefulness and in controlling the occurrence of state of active sleep...
  81. ncbi Involvement of spinal GABA receptors in the regulation of intraspinal acetylcholine release
    Mahinda Kommalage
    Department of Neuroscience, Division of Comparative Medicine, Uppsala University, BMC, Box 572, S 75123, Uppsala, Sweden
    Eur J Pharmacol 525:69-73. 2005
    ..The results suggest that both GABA receptor subtypes have an inhibitory role on spinal dorsal horn acetylcholine release and that the GABA(A) receptors are tonically regulating acetylcholine release...
  82. ncbi GABA and development of the Xenopus optic projection
    Shane C D Ferguson
    Genes and Development Research Group, University of Calgary, AB, Canada
    J Neurobiol 51:272-84. 2002
    ..These data indicate that GABA may act in vivo to stimulate the outgrowth of Xenopus RGC axons along the optic tract...
  83. pmc Peripheral GABAB agonists stimulate gastric acid secretion in mice
    Laura Piqueras
    Department of Physiology, Pharmacology and Toxicology, Cardenal Herrera CEU University, Valencia, Spain
    Br J Pharmacol 142:1038-48. 2004
    ..Somatostatin implication might be secondary to the release of gastrin and the increase in gastric luminal acidity...
  84. ncbi Development of GABAergic and glycinergic transmission in the neonatal rat dorsal horn
    Mark L Baccei
    Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom
    J Neurosci 24:4749-57. 2004
    ..GABA(A)R-mediated depolarizations during the first postnatal week are likely to be important for the maturation of spinal networks but do not provide a major excitatory drive to the newborn dorsal horn...
  85. ncbi GABA(B) receptor-activation inhibits GABAergic synaptic transmission in parvocellular neurones of rat hypothalamic paraventricular nucleus
    X Liu
    Department of Basic Neuroscience, University Medical Centre, Geneva, Switzerland
    J Neuroendocrinol 18:177-86. 2006
    ..Activation of these receptors causes disinhibition of parvocellular neurosecretory and nonendocrine paraventricular neurones...
  86. ncbi GABAergic and glycinergic inhibitory mechanisms in the lamprey respiratory control
    Fulvia Bongianni
    Dipartimento di Scienze Fisiologiche, Universita degli Studi di Firenze, Viale G B Morgagni 63, I 50134 Firenze, Italy
    Brain Res 1090:134-45. 2006
    ....
  87. ncbi GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression
    Alexandre Serrano
    Centre de Recherche en Sciences Neurologiques, Departement de Physiologie, Universite de Montreal, Succursale Centre Ville, Montreal, Quebec, H3C 3J7, Canada
    J Neurosci 26:5370-82. 2006
    ..Thus, glial and neuronal networks are functionally associated during the genesis of heterosynaptic plasticity at mammalian central excitatory synapses...
  88. ncbi Regulation of cardiac sympathetic afferent reflex by GABA(A) and GABA(B) receptors in paraventricular nucleus in rats
    Ming Kui Zhong
    Departments of Physiology and Biochemical and Molecular Biology, Nanjing Medical University, Nanjing, China
    Eur J Neurosci 27:3226-32. 2008
    ..Endogenous GABA in the PVN could have an important role in regulating CSAR...
  89. ncbi Functional GABA(B) receptors are expressed at the cone photoreceptor terminals in bullfrog retina
    J Liu
    Institute of Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200433, China
    Neuroscience 132:103-13. 2005
    ....
  90. pmc Activation of postsynaptic GABAB receptors modulates the bursting pattern and synaptic activity of olfactory bulb juxtaglomerular neurons
    Nikolay Karpuk
    Deptepartment of Neurobiology and Developmental Sciences, Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Neurophysiol 99:308-19. 2008
    ..Thus the postsynaptic GABA(B)-Rs on ET cells may play an important role in shaping the activation pattern of the glomeruli during olfactory coding...
  91. ncbi gamma-Aminobutyric acid receptor subtype antagonists differentially alter opioid-induced feeding in the shell region of the nucleus accumbens in rats
    V Znamensky
    Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, City University of New York, 65--30 Kissena Boulevard, Flushing, NY 11367, USA
    Brain Res 906:84-91. 2001
    ..These data indicate that GABA(A) and GABA(B) receptor subtype antagonists differentially affect feeding elicited by mu opioid receptor agonists within the nucleus accumbens shell in rats...
  92. ncbi Role of GABA(B) receptor in the regulation of excitatory synaptic transmission in trigeminal motoneurons
    Ming Yuan Min
    Department of Physiology, Chinese Medical College, Taichung, Taiwan, ROC
    J Biomed Sci 9:348-58. 2002
    ..Taken together the above results suggest that the excitatory synaptic inputs onto trigeminal motoneurons are controlled by tonic presynaptic modulation by GABA(B) receptor...
  93. ncbi GABAergic modulation of primary gustatory afferent synaptic efficacy
    Andrew A Sharp
    Department of Cellular and Structural Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Neurobiol 52:133-43. 2002
    ..The mechanism of action of GABA(B) receptors suggests a presynaptic locus of action for that receptor...
  94. ncbi Analysis of the function of GABA(B) receptors on inhibitory afferent neurons of Purkinje cells in the cerebellar cortex of the rat
    Marta Than
    Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Albertstrasse 25, D 79104 Freiburg i Br, Germany
    Eur J Neurosci 15:1575-84. 2002
    ....
  95. ncbi Synaptic activation of GABA(B) receptors regulates neuronal network activity and entrainment
    Jon T Brown
    Neurology and GI, GlaxoSmithKline, Harlow, Essex, UK
    Eur J Neurosci 25:2982-90. 2007
    ..Furthermore, the flow of such information into a functioning neuronal network is highly regulated by GABA(B) receptor-mediated synaptic inhibition...
  96. ncbi GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts
    E M Mintz
    Department of Biological Sciences, Youngstown State University, OH 44555, USA
    Neuroscience 109:773-8. 2002
    ..These data suggest that GABA regulates the phase of the circadian clock through both pre- and postsynaptic mechanisms...
  97. pmc GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior
    Stacey C LaGraize
    Department of Psychology, University of Texas at Arlington, Arlington, TX 76019, USA
    Exp Neurol 204:182-94. 2007
    ..These results provide additional support for the role of the rACC in higher order supraspinal processing of noxious events and suggest that rACC GABA(A) receptors significantly contribute to this processing...
  98. ncbi GABA(B) receptors in the median raphe nucleus: distribution and role in the serotonergic control of hippocampal activity
    V Varga
    National Institute of Neurosurgery, Budapest, Hungary
    Neuroscience 109:119-32. 2002
    ..Our data indicate that midbrain raphe GABA(B) mechanisms play an important role in behavioral state control and in hippocampal activity, in particular...
  99. ncbi GABA(A) and GABA(B) receptors in the anterior piriform cortex modulate feeding in rats
    Ban G Truong
    Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    Brain Res 924:1-9. 2002
    ..Taken together, these results support the involvement of GABA receptors in the APC in feeding in general and the responses to amino acid deprivation in vivo...
  100. ncbi Presynaptic GABA(B) receptors inhibit synaptic inputs to rat subthalamic neurons
    K Z Shen
    Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, USA
    Neuroscience 108:431-6. 2001
    ..These results provide evidence for presence of presynaptic GABA(B) receptors that modulate both GABA and glutamate release from afferent terminals in the subthalamus...
  101. ncbi Effects of GABA(A) and GABA(B) agonists on interhemispheric inhibition in man
    K Irlbacher
    Vision and Motor Group, Department of Neurology, Charite, Humboldt University of Berlin, Campus Mitte, Schumannstrasse 20 21, D 10117 Berlin, Germany
    Clin Neurophysiol 118:308-16. 2007
    ..In humans the mechanism is unclear. Interactions between cortical inhibitory circuits suggest a postsynaptic GABA(B)-ergic mechanism. We will here test this hypothesis...

Research Grants62

  1. GHB Tolerance and Dependence
    Cynthia Kuhn; Fiscal Year: 2006
    ..These experiments should ultimately lead to the development of more effective pharmacotherapies for GHB dependence, which is an emerging drug abuse problem. ..
  2. The GABA-B receptor is a novel drug target for pancreatic cancer
    Hildegard M Schuller; Fiscal Year: 2012
    ..Since GABA and baclophen are already approved for the treatment of non-cancerous conditions in humans, results of this research can be rapidly translated into clinical trials. ..
  3. Neurobiological studies of gammahydroxybutyrate
    Thomas S Kilduff; Fiscal Year: 2012
    ..We will exploit a mouse model of narcolepsy in which the Hcrt neurons degenerate postnatally as they do in human narcoleptics to understand how GHB is beneficial in human narcolepsy. ..
  4. ROLE OF INHIBITION WITHIN THE CEREBELLAR NODULUS/UVULA IN VESTIBULAR PROCESSING
    TATYANA ALEKSANDROVNA YAKUSHEVA; Fiscal Year: 2012
    ....
  5. GABA-B Receptor Modulation of Calcium Currents
    Michelle Mynlieff; Fiscal Year: 2010
    ..but these compounds also cause side effects such as drowsiness, mental slowing, and double vision. By increasing our understanding of the specific effects of GABA, it will be possible to design better drugs for these types of disorders. ..
  6. Anesthetic actions on GABA(A) fast, slow, tonic and GABA(B) receptors
    M Bruce MacIver; Fiscal Year: 2013
    ..As the GABA receptor subtypes underlying various forms of inhibition become known, our results will help link desired and unwanted anesthetic effects to these molecular targets. ..
  7. A Sensory Map for Sulfated Steroids in the Accessory Olfactory Bulb
    Gary Hammen; Fiscal Year: 2013
    ..These studies in the accessory olfactory system will record functional information from all sensory neurons in the accessory olfactory system, providing a broad perspective from which to form hypotheses about sensory processing. ..
  8. Ischemic Spasticity: Modulation by GAD65 Gene Delivery
    Martin Marsala; Fiscal Year: 2010
    ....
  9. Basal forebrain and cognitive aging: Novel experimental and theraptutic avenues
    JENNIFER LYNN BIZON; Fiscal Year: 2011
    ..Finally, we will treat middle-aged and aged rats with cholinergic and GABAergic drugs, both separately and in concert, to reverse age-related cognitive impairments. ..
  10. Development of GABABeta Receptor Compounds for Nicotine Dependence
    Athina Markou; Fiscal Year: 2013
    ..This multidisciplinary research program integrates the complementary expertise of the participating scientists to provide innovative potential therapeutics for nicotine dependence in humans. ..
  11. A Translational Investigation of Anhedonia and its Underlying Neural Mechanisms
    Andre Der Avakian; Fiscal Year: 2010
    ..Such models will greatly facilitate 1) our understanding of the underlying neurobiological mechanisms that are involved and 2) the discovery of novel pharmacotherapies that target these mechanisms. ..
  12. Phase II Trial of SGS-742 in Succinic Semialdehyde Dehydrogenase Deficiency
    K Michael Gibson; Fiscal Year: 2013
    ..The project's long term significance centers on identification of effective treatment for SSADH deficiency and related disorders in which neurocognitive dysfunction correlates with GABAergic systems. ..
  13. Intrathecal Delivery of GABAmide to Reduce Spasticity
    Jay Meythaler; Fiscal Year: 2001
    ..Development of a more effective alternative to intrathecally-delivered baclofen would allow for a significant profit and still decrease the cost of this effective treatment system. ..
  14. Enzyme & Receptor Antagonists of GHB, GBL & 1, 4-BD
    Lawrence Quang; Fiscal Year: 2003
    ..The results of this study will expand upon promising data from pilot studies performed in this laboratory on acute 1,4-BD and GHB toxicity as well as novel therapeutic agents for its potential medical management. ..
  15. OPIOID GABA INTERACTIONS AND ANTINOCICEPTION
    Alexander Kalyuzhny; Fiscal Year: 2002
    ..Results of this study will contribute to our understanding of the mechanisms of opioid anti-nociception, and will suggest strategies for developing alterative, non-opioid, approaches for pain-treatment. ..
  16. A NOVEL CLASS OF MAMMALIAN GABA RECEPTOR
    Ricardo Miledi; Fiscal Year: 1993
    ....
  17. Drug-Induced Motor Recovery After Spinal Cord Injury
    Kwaku Nantwi; Fiscal Year: 2005
    ..abstract_text> ..
  18. Communication within the Suprachiasmatic Neural Circadian Network
    ELLIOTT H ALBERS; Fiscal Year: 2013
    ..Understanding how GABA acts in the brain is extremely important clinically because of the many drugs that target GABA receptors for diseases ranging from epilepsy to anxiety. ..
  19. Direct Interaction Between GABA-A and GABA-B Receptors
    Randy Hall; Fiscal Year: 2007
    ..abstract_text> ..
  20. SYNAPTIC ORGANIZATION OF RETROHIPPOCAMPAL PATHWAYS
    David Finch; Fiscal Year: 1991
    ..Specific antagonists of GABA A and GABA B receptors will be used in order to determine the receptor subtype(s) responsible for the inhibitory responses...
  21. Rapid Effects of Estradiol in the Brain
    Jill Becker; Fiscal Year: 2007
    ..It may also be important for our understanding and treatment of a number of neurological disorders including stroke, Alzheimer's disease and Parkinson's disease where estradiol may be neuroprotective. ..
  22. TRANSMEMBRANE SIGNALING AT GABA RECEPTORS
    WALTER WOJCIK; Fiscal Year: 1990
    ....
  23. SYNAPTIC CONNECTIVITY IN THE DENTATE GYRUS
    HILLARY MICHELSON; Fiscal Year: 2003
    ..Together, these studies should provide valuable information describing the generation of the opioid-dependent granule cell depolarization, and its involvement in normal and pathophysiologic synaptic transmission in the hippocampus. ..
  24. G-protein signal coordination by RGS12
    DAVID SIDEROVSKI; Fiscal Year: 2009
    ..We wish to study one RGS protein, RGS12, that interferes with the actions of the neurotransmitter GABA in neurons that control pain processing. This work should lead to the discovery of new pain-controlling drugs. ..
  25. GABA-B Receptors as Regulators of Islet Biology
    Kathleen Dunlap; Fiscal Year: 2003
    ..Understanding the natural biological mechanisms by which islets are regulated is prerequisite to harnessing them for the development of new treatment strategies for diabetes. ..
  26. CONTROL OF NOCICEPTION BY GABA
    Donna Hammond; Fiscal Year: 1993
    ..raphe magnus. The results of these studies will provide new insights into non-opioid mechanisms of antinociception...
  27. CREB Mediated GABA-B Receptor Regulation in the Nucleus Accumbens
    SOPHIE DESBIENS; Fiscal Year: 2009
    ..Then, we will the address whether R1a and R1b regulation in the NAc is affected by chronic baclofen treatment (Aim 2) and in a rat model of cocaine self-administration (Aim 3). ..
  28. Role of GABA in the locomotor effects of ethanol.
    SARAH HOLSTEIN; Fiscal Year: 2006
    ..As acute sensitivity to ethanol's stimulant effects is suggested to be a predictor of later addiction, it is important to elucidate the neurobiological and genetic mechanisms underlying this trait. ..
  29. Neuropharmacology of GHB discrimination
    Wouter Koek; Fiscal Year: 2010
    ..Increased knowledge about the activation and modulation of GABAB systems will help to develop effective approaches to treating sleep-, drug abuse-, and other CNS disorders. ..
  30. Discriminative Stimulus Effects of Alcohol in Mice
    Wouter Koek; Fiscal Year: 2007
    ..This future research will increase our understanding of risk factors for alcoholism and drug abuse and will help the development of effective approaches to prevention and treatment. [unreadable] [unreadable] [unreadable]..
  31. MOP Receptor Effects on the Hippocampal CA1 Network
    ADAM MCQUISTON; Fiscal Year: 2008
    ..The results from these studies will provide important information regarding MOP receptor-induced changes in network activity and may possibly lead to the development of treatments for opioid addiction. ..
  32. OPIOID EFFECTS ON HYPOTHALAMIC NEURONAL EXCITABILITY
    Martin Kelly; Fiscal Year: 2002
    ....
  33. Alcohol Sensitivity and PET Derived Measures of Opioid Activity
    Elise M Weerts; Fiscal Year: 2010
    ..The results of the proposed research will increase our understanding of to the relationship between individual variability in the opioid system and subjective sensitivity to alcohol. ..
  34. Cue-Reactivity and Alcohol Self-Dosing
    Elise Weerts; Fiscal Year: 2003
    ..This research will additionally provide important information on the behavioral processes underlying conditioned responses to drug-related cues in animals which may be relevant to cue-reactivity and drug-taking in humans. ..
  35. Behavioral Pharmacology and GHB Physical Dependence
    Elise M Weerts; Fiscal Year: 2010
    ..Physical dependence in the context of self-injection of GHB, GBL and 1,4-BD will also be evaluated. These studies will provide critical information on the behavioral pharmacology and dependence-producing effects of GHB. ..
  36. Prenatal Virally Induced Brain Disorder in Mouse
    SEYYED FATEMI; Fiscal Year: 2009
    ..In addition, it is expected that the results will provide clues that will lead to fundamental advances in our knowledge of the pathogenesis of schizophrenia and, therefore, of how it can be prevented and treated. ..
  37. Varenicline and Smoking Cessation in Schizophrenia
    SEYYED HOSSEIN FATEMI; Fiscal Year: 2010
    ..Such outcomes will be significant, because they will offer a new treatment for smoking cessation in this vulnerable population. ..
  38. Studies on the role of GABA in Cocaine Addiction
    Elise Weerts; Fiscal Year: 2005
    ..The results of these studies will increase our understanding of the role of GABA in the behavioral effects of cocaine and may lead to the development of better medications for the treatment of cocaine addiction. ..
  39. Preclin. model for prevention of NSCLC in former smokers
    HILDEGARD SCHULLER; Fiscal Year: 2006
    ....
  40. Mechanisms Underlying the Cognitive Function of Sleep
    Subimal Datta; Fiscal Year: 2009
    ....
  41. NNK, Beta-Adrenergic AA Release and Lung Cancer
    HILDEGARD SCHULLER; Fiscal Year: 2005
    ..2. To determine which products of the AA cascade are formed in untreated cells and in response to NNK, which of these products stimulate DNA synthesis, and what downstream effectors are activated by these products. ..
  42. Lateral Hypothalamus, Dopamine and Ingestive Behavior
    David Wirtshafter; Fiscal Year: 2007
    ..Gaining an understanding of these systems is a prerequisite for the rational development of novel treatments for disturbances of ingestion, such as occur in obesity, bulemia and cahchexia. [unreadable] [unreadable] [unreadable]..
  43. DEVELOPMENT OF THE CORTICOTHALAMIC SYSTEM
    Edward Jones; Fiscal Year: 2003
    ..Defective maturation may be a concomitant of or a basis for certain forms of seizures in young individuals. ..
  44. Chemoanatomic bases for peripheral vestibular function
    GAY HOLSTEIN; Fiscal Year: 2007
    ..The proposed research is unique, and will have direct bearing on the development of more effective therapeutic interventions, both medicinal and device-oriented, for peripheral vestibular disorders. [unreadable] [unreadable] [unreadable]..
  45. Submissive Behavior as a Model of Depression
    Godfrey Tunnicliff; Fiscal Year: 2002
    ..The identification of genetic elements in mice associated with depression-like behavior can be tested for homology in human patients that could ultimately lead to an understanding of genetic defects underlying depression in humans. ..
  46. Mechanisms of Signal Transduction of GHB Action
    Godfrey Tunnicliff; Fiscal Year: 2002
    ..In turn, this will help to develop therapeutic and preventive strategies resulting in a lessened abuse potential of GHB. ..
  47. Proposed Role for Neuronal Serotonin N-acetyltransferase
    Hari Manev; Fiscal Year: 2006
    ..We expect the results to elucidate the role of AANAT/NAS in neuronal functioning, and in the long term, in the pathobiology of depression. ..
  48. MORPHOLOGIC BASIS FOR CENTRAL VESTIBULAR INHIBITION
    GAY HOLSTEIN; Fiscal Year: 2002
    ....
  49. ALTERING BEHAVIORAL RISK FOR DRUG DEPENDENCE
    DON CHEREK; Fiscal Year: 2001
    ..Pharmacological effects of these therapeutics drugs on such behavior in a high risk population may provide information relating to alternative strategies in dealing with drug dependence. ..
  50. Alcohol Modulation of Cerebellar Synaptic Currents
    William Proctor; Fiscal Year: 2006
    ..The combination of our proposed and ongoing genetic studies may aid the identification of more sensitive drug targets and the development of novel drugs for rational therapeutic approaches to alcoholism. ..
  51. Preventing spike-wave epileptogenesis: critical periods & neuroimaging biomarkers
    Hal Blumenfeld; Fiscal Year: 2010
    ..untreated animals. We will also investigate the anatomical basis of white matter DTI abnormalities through electron microscopy to determine changes in axons and myelin in affected regions. 2. ..
  52. Estrogen modulation of hypothalamic arcuate neurons
    Anna Malyala; Fiscal Year: 2006
    ..Finally, I will determine the function of the PI3K pathway in estrogen signaling in POMC arcuate neurons using whole-cell recordings. ..
  53. Retinal Synaptic Transmission: Channels and Transmitters
    Zhuo Hua Pan; Fiscal Year: 2005
    ..The understanding of the role of voltage-activated Ca2+ channels in synaptic transmission may also provide insight for identifying the mechanism of diseases caused by synaptic dysfunction. ..
  54. Deciphering genes and pathways in nicotine dependence
    Ming Li; Fiscal Year: 2008
    ..The completion of the proposed studies will advance our understanding of complex gene expression patterns associated with nicotine dependence and nicotine withdrawal in rats and in human postmortem brain tissues. ..
  55. GABAA RECEPTOR BETA-SUBUNIT AND GENERAL ANESTHETICS
    Jay Yang; Fiscal Year: 2002
    ..The experiments proposed will add quantitative and mechanistic information to general anesthetic molecular pharmacology and move this field of investigation closer towards truly understanding how these clinically essential drugs work. ..
  56. 5HT transporter & 1A receptor function in BDNF mice
    JULIE HENSLER; Fiscal Year: 2007
    ..Region-specific and age-dependent changes in BDNF protein levels will be determined in selected brain regions of wild-type and BDNF () mice (Aim #3). [unreadable] [unreadable] [unreadable]..
  57. CRF and Personality Disorder: Behavioral Correlates
    Royce Lee; Fiscal Year: 2003
    ..abstract_text> ..
  58. REGULATION OF MESOLIMBIC DOPAMINE BY ENDOGENOUS COMPOUND
    Peter Kalivas; Fiscal Year: 2003
    ..Furthermore, the anatomical and functional mapping of the motive circuit will provide a basis for interpreting future imaging studies in humans where attempts are made to correlate changes in spatially discrete nuclei. ..
  59. GABA Modulation of Cocaine & Heroin Self-Administration
    David Roberts; Fiscal Year: 2003
    ..The degree to which either IP or intracerebral injections of baclofen affect heroin self-administration will also be assessed. ..
  60. BASAL GANGLIA CIRCUITRY IMMEDIATE EARLY GENE EXPRESSION
    David Wirtshafter; Fiscal Year: 2003
    ..Other studies will examine the effects of lesions within the basal ganglia on the IEG expression induced by systemic administration of dopaminergic drugs. ..
  61. Correlation Among Retinal Directionally Selective Cells
    NORBERTO GRZYWACZ; Fiscal Year: 2005
    ..Retinal binding defects may contribute to some of these integrative problems, but even if not, retinal strategies and mechanisms may shed light on mechanisms in other areas of the brain. ..