Recent advances in molecular biology and complementary information derived from neuropharmacology, biochemistry and behavior have dramatically increased our understanding of various aspects of GABA
receptors. These studies have revealed that the GABA
. Furthermore, two additional subunits (β
receptors in chick brain, and five isoforms of the ρ-subunit in the retina of white perch (
) have been identified. Various techniques such as mutation, gene knockout and inhibition of GABA
receptor subunits by antisense oligodeoxynucleotides have been used to establish the physiological/pharmacological significance of the GABA
receptor subunits and their native receptor assemblies in vivo. Radioligand binding to the immunoprecipitated receptors, co-localization studies using immunoaffinity chromatography and immunocytochemistry techniques have been utilized to establish the composition and pharmacology of native GABA
receptor assemblies. Partial agonists of GABA
receptors are being developed as anxiolytics which have fewer and less severe side effects as compared to conventional benzodiazepines because of their lower efficacy and better selectivity for the GABA
receptor subtypes. The subunit requirement of various drugs such as anxiolytics, anticonvulsants, general anesthetics, barbiturates, ethanol and neurosteroids, which are known to elicit at least some of their pharmacological effects via the GABA
receptors, have been investigated during the last few years so as to understand their exact mechanism of action. Furthermore, the molecular determinants of clinically important drug-targets have been investigated. These aspects of GABA
receptors have been discussed in detail in this review article.
Cited by: | - Weaver, Ian C.G.; La Plante, Patricia; Weaver, Shelley; Parent, Angel; Sharma, Shakti; Diorio, Josie; Chapman, Karen E.; Seckl, Jonathan R.; Szyf, Moshe; Meaney, Michael J.,""Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites""Molecular and Cellular Endocrinology2001pp. 205-218
Bibliographic PageFull Text - Lech, Monika; Skibinska, Anna; Kossut, Malgorzata,""Delayed upregulation of GABAA alpha1 receptor subunit mRNA in somatosensory cortex of mice following learning-dependent plasticity of cortical representations""Molecular Brain Research2001pp. 82-86
Bibliographic PageFull Text - Huang, Ren-Qi; Dillon, Glenn H.,""Functional analysis of GABAA receptors in nucleus tractus solitarius neurons from neonatal rats""Brain Research2001pp. 183-194
Bibliographic PageFull Text - Fonfria, E.; Rodriguez-Farre, E.; Sunol, C.,""Mercury interaction with the GABAA receptor modulates the benzodiazepine binding site in primary cultures of mouse cerebellar granule cells""Neuropharmacology2001pp. 819-833
Bibliographic PageFull Text - Rinaldi, Daisy; Larrigaldie, Vanessa; Chapouthier, Georges; Martin, Benoit,""Unexpected absence of correlation between the genetic mechanisms regulating b-carboline-induced seizures and anxiety manifested in an elevated plus-maze test""Behavioural Brain Research2001pp. 159-165
Bibliographic PageFull Text - Jardim, Marcelo Cesar; Guimaraes, Francisco Silveira,""GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial hypothalamus""Pharmacology Biochemistry and Behavior2001pp. 579-584
Bibliographic PageFull Text - Ratra, Gurpreet S.; Casida, John E.,""GABA receptor subunit composition relative to insecticide potency and selectivity""Toxicology Letters2001pp. 215-222
Bibliographic PageFull Text - Follesa, Paolo; Cagetti, Elisabetta; Mancuso, Luisa; Biggio, Francesca; Manca, Annalisa; Maciocco, Elisabetta; Massa, Federico; Speranza Desole, Maria; Carta, Mario; Busonero, Fabio; Sanna, Enrico; Biggio, Giovanni,""Increase in expression of the GABAA receptor a4 subunit gene induced by withdrawal of, but not by long-term treatment with, benzodiazepine full or partial agonists""Molecular Brain Research2001pp. 138-148
Bibliographic PageFull Text - Smith, Yoland; Charara, Ali; Paquet, Maryse; Kieval, Jeremy Z.; Pare, Jean-Francois; Hanson, Jesse E.; Hubert, George W.; Kuwajima, Masaaki; Levey, Allan I.,""Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia""Journal of Chemical Neuroanatomy2001pp. 13-42
Bibliographic PageFull Text - Forster, Ian C.; Harvey, Robert J.; Darlison, Mark G.; Benson, Jack A.,""Functional pharmacology of GABAA receptors containing the chicken brain g4 subunit""European Journal of Pharmacology2001pp. 1-7
Bibliographic PageFull Text - Pignataro, Leonardo; Fiszer de Plazas, Sara,""In ovo chronic neurosteroid treatment affects the function and allosteric interactions of GABAA receptor modulatory sites""Brain Research2001pp. 74-81
Bibliographic PageFull Text - Mehta, Ashok K.; Ticku, Maharaj K.,""Unsulfated and sulfated neurosteroids differentially modulate the binding characteristics of various radioligands of GABAA receptors following chronic ethanol administration""Neuropharmacology2001pp. 668-675
Bibliographic PageFull Text - Verleye, M.; Schlichter, R.; Neliat, G.; Pansart, Y.; Gillardin, J.M.,""Functional modulation of gamma-aminobutyric acidA receptors by etifoxine and allopregnanolone in rodents""Neuroscience Letters2001pp. 191-194
Bibliographic PageFull Text - Saba, L.; Porcella, A.; Congeddu, E.; Colombo, G.; Peis, M.; Pistis, M.; Gessa, G.L.; Pani, L.,""The R100Q mutation of the GABAA a6 receptor subunit may contribute to voluntary aversion to ethanol in the sNP rat line1""Molecular Brain Research2001pp. 263-270
Bibliographic PageFull Text - Mikkelsen, Jens D.; Karle, Jesper; Madsen, Torsten M.,""Intrahippocampal infusion of antisense oligodeoxynucleotide to the GABAA receptor g2 subunit enhances neuropeptide Y gene expression""Brain Research Bulletin2001pp. 91-99
Bibliographic PageFull Text - Li, Ming; Szabo, Andras; Rosenberg, Howard C.,""Evaluation of native GABAA receptors containing an a5 subunit""European Journal of Pharmacology2001pp. 63-72
Bibliographic PageFull Text - Martijena, Irene D.; Lacerra, Carolina; Bustos, Silvia G.; Molina, Victor A.,""Chronic benzodiazepine administration facilitates the subsequent development of ethanol dependence""Brain Research2001pp. 236-246
Bibliographic PageFull Text - Ratra, Gurpreet S.; Kamita, S. George; Casida, John E.,""Role of Human GABAA Receptor b3 Subunit in Insecticide Toxicity""Toxicology and Applied Pharmacology2001pp. 233-240
Bibliographic PageFull Text - Bianchi, M.T.; Haas, K.F.; Macdonald, R.L.,""a1 and a6 subunits specify distinct desensitization, deactivation and neurosteroid modulation of GABAA receptors containing the d subunit""Neuropharmacology2002pp. 492-502
Bibliographic PageFull Text - Yang, Paul; Jones, Brian L.; Henderson, Leslie P.,""Mechanisms of anabolic androgenic steroid modulation of a1b3g2L GABAA receptors""Neuropharmacology2002pp. 619-633
Bibliographic PageFull Text - McIntyre, K.L.; Porter, D.M.; Henderson, L.P.,""Anabolic androgenic steroids induce age-, sex-, and dose-dependent changes in GABAA receptor subunit mRNAs in the mouse forebrain""Neuropharmacology2002pp. 634-645
Bibliographic PageFull Text - Gulinello, M.; Gong, Q.H.; Smith, S.S.,""Progesterone withdrawal increases the a4 subunit of the GABAA receptor in male rats in association with anxiety and altered pharmacology - a comparison with female rats""Neuropharmacology2002pp. 701-714
Bibliographic PageFull Text - Guyon, Alice; Cathala, Laurence; Paupardin-Tritsch, Daniele; Eugene, Daniel,""Furosemide modulation of GABAA receptors in dopaminergic neurones of the rat substantia nigra""Neuropharmacology2002pp. 750-763
Bibliographic PageFull Text - Navarro, Jose Francisco; Buron, Estrella; Martin-Lopez, Mercedes,""Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine site of GABAA receptors which contain the alpha-5 subunit, in the elevated plus-maze test""Progress in Neuro-Psychopharmacology and Biological Psychiatry2002pp. 1389-1392
Bibliographic PageFull Text - Wilkins, M.E.; Smart, T.G.,""Redox modulation of GABAA receptors obscured by Zn2+ complexation2""Neuropharmacology2002pp. 938-944
Bibliographic PageFull Text - Nelson, Rachael M.; Green, A. Richard; Hainsworth, Atticus H.,""Electrophysiological actions of g-aminobutyric acid and clomethiazole on recombinant GABAA receptors""European Journal of Pharmacology2002pp. 255-262
Bibliographic PageFull Text - Verleye, Marc; Pansart, Yannick; Gillardin, Jean-Marie,""Effects of etifoxine on ligand binding to GABAA receptors in rodents""Neuroscience Research2002pp. 167-172
Bibliographic PageFull Text - Mu, Weitong; Cheng, Qing; Yang, Jay; Burt, David R.,""Alternative splicing of the GABAA receptor a4 subunit creates a severely truncated mRNA""Brain Research Bulletin2002pp. 447-454
Bibliographic PageFull Text - Akhondzadeh, Shahin; Mohammadi, Mohammad Reza; Kashani, Ladan,""Potentiation of muscimol-induced long-term depression by benzodiazepines but not zolpidem""Progress in Neuro-Psychopharmacology and Biological Psychiatry2002pp. 1161-1166
Bibliographic PageFull Text - Calon, Frederic; Di Paolo, Therese,""Levodopa response motor complications-GABA receptors and preproenkephalin expression in human brain""Parkinsonism and Related Disorders2002pp. 449-454
Bibliographic PageFull Text - Zhang, Zhang-Jin; Postma, Terri; Obeng, Kris; Russell, Shani; Weiss, Susan R.B.; Post, Robert M.,""The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats""Neuroscience Letters2002pp. 253-256
Bibliographic PageFull Text - Borowicz, Kinga K.; Zadrozniak, Marek; ader, Mariusz; Kowalska, Aneta; Kleinrok, Zdzislaw; Czuczwar, Stanislaw J.,""Interaction of the neurosteroid alphaxalone with conventional antiepileptic drugs in different types of experimental seizures""European Journal of Pharmacology2002pp. 85-90
Bibliographic PageFull Text - Pattij, Tommy; Groenink, Lucianne; Oosting, Ronald S.; van der Gugten, Jan; Maes, Robert A.A.; Olivier, Berend,""GABAA-benzodiazepine receptor complex sensitivity in 5-HT1A receptor knockout mice on a 129/Sv background""European Journal of Pharmacology2002pp. 67-74
Bibliographic PageFull Text - Le Corronc, Herve; Alix, Philippe; Hue, Bernard,""Differential sensitivity of two insect GABA-gated chloride channels to dieldrin, fipronil and picrotoxinin""Journal of Insect Physiology2002pp. 419-431
Bibliographic PageFull Text - Gerasimov, M.R.; Ferrieri, R.A.; Schiffer, W.K.; Logan, J.; Gatley, S.J.; Gifford, A.N.; Alexoff, D.A.; Marsteller, D.A.; Shea, C.; Garza, V.; Carter, P.; King, P.; Ashby Jr, C.R.; Vitkun, S.; Dewey, S.L.,""Study of brain uptake and biodistribution of [11C]toluene in non-human primates and mice""Life Sciences2002pp. 2811-2828
Bibliographic PageFull Text - Kalluri, Haviryaji S.G.; Ticku, Maharaj K.,""Ethanol-mediated inhibition of mitogen-activated protein kinase phosphorylation in mouse brain""European Journal of Pharmacology2002pp. 53-58
Bibliographic PageFull Text - Martin, Joseph V.; Bilgin, Nesli M.; Iba, M. Michael,""Influence of oxygenated fuel additives and their metabolites on the binding of a convulsant ligand of the g-aminobutyric acidA (GABAA) receptor in rat brain membrane preparations""Toxicology Letters2002pp. 219-226
Bibliographic PageFull Text - LaBuda, Christopher J.; Fuchs, Perry N.,""Catecholamine depletion by reserpine blocks the anxiolytic actions of ethanol in the rat""Alcohol2002pp. 55-59
Bibliographic PageFull Text - Nemmani, Kumar V.S.; Ramarao, P.,""Role of benzodiazepine-GABAA receptor complex in attenuation of U-50,488H-induced analgesia and inhibition of tolerance to its analgesia by ginseng total saponin in mice""Life Sciences2002pp. 1727-1740
Bibliographic PageFull Text - Follesa, P.; Mancuso, L.; Biggio, F.; Cagetti, E.; Franco, M.; Trapani, G.; Biggio, G.,""Changes in GABAA receptor gene expression induced by withdrawal of, but not by long-term exposure to, zaleplon or zolpidem""Neuropharmacology2002pp. 191-198
Bibliographic PageFull Text - Shumsky, Jed S.; Wu, Yunxing; Murphy, E. Hazel; Nissanov, Jonathan; O'Brien-Jenkins, Ann; Grayson, Dennis R.,""Differential effects of prenatal cocaine exposure on selected subunit mRNAs of the GABAA receptor in rabbit anterior cingulate cortex""Journal of Chemical Neuroanatomy2002pp. 243-255
Bibliographic PageFull Text - OBRADOVIC, DRAGAN I.; BOKONJIC, DUBRAVKO R.; SAVIC, MIROSLAV M.; ANDJELKOVIC, DRAGINJA S.; UGRESIC, NENAD D.; STOJILJKOVIC, MILOS P.,""GABA-BENZODIAZEPINE RECEPTOR COMPLEX IN BRAIN OXIDATIVE METABOLISM REGULATION""Pharmacological Research2002pp. 149-154
Bibliographic PageFull Text - Fujimori, Sayumi; Hinoi, Eiichi; Yoneda, Yukio,""Functional GABAB receptors expressed in cultured calvarial osteoblasts""Biochemical and Biophysical Research Communications2002pp. 1445-1452
Bibliographic PageFull Text - Fisher, Janet L.,""A Lysine Residue in the b3 Subunit Contributes to the Regulation of GABAA Receptor Activity by Voltage""Molecular and Cellular Neuroscience2002pp. 683-694
Bibliographic PageFull Text - Krehan, Dorte; Frolund, Bente; Krogsgaard-Larsen, Povl; Kehler, Jan; Johnston, Graham A.R.; Chebib, Mary,""Phosphinic, phosphonic and seleninic acid bioisosteres of isonipecotic acid as novel and selective GABAC receptor antagonists""Neurochemistry International2003pp. 561-565
Bibliographic PageFull Text - Barros, Pedro Henrique Oliveira Cavalcanti; Calaza, Karin da Costa; Gardino, Patricia Franca,""GABAAb2-3 immunoreactive cells in the developing chick retina""International Journal of Developmental Neuroscience2003pp. 35-40
Bibliographic PageFull Text - Nishiguchi, Mariko; Tokugawa, Kimiko; Yamamoto, Kyoko; Akama, Tomoko; Nozawa, Yuriko; Chaki, Shigeyuki; Ueki, Tomokazu; Kameo, Kazuya; Okuyama, Shigeru,""Increase in secretion of glial cell line-derived neurotrophic factor from glial cell lines by inhibitors of vacuolar ATPase""Neurochemistry International2003pp. 493-498
Bibliographic PageFull Text - Sanna, Angela; Congeddu, Elena; Porcella, Anna; Saba, Luisella; Pistis, Marco; Peis, Michela; Marchese, Giorgio; Ruiu, Stefania; Lobina, Carla; Grayson, Dennis R.; Gessa, Gian Luigi; Pani, Luca,""Characterization of wild-type (R100R) and mutated (Q100Q) GABAA a6 subunit in Sardinian alcohol non-preferring rats (sNP)""Brain Research2003pp. 98-105
Bibliographic PageFull Text - van Rijn, Clementina M.; Willems-van Bree, Elly,""Synergy between retigabine and GABA in modulating the convulsant site of the GABAA receptor complex""European Journal of Pharmacology2003pp. 95-100
Bibliographic PageFull Text - Van De Berg, W.D.J.; Kwaijtaal, M.; De Louw, A.J.A.; Lissone, N.P.A.; Schmitz, C.; Faull, R.L.M.; Blokland, A.; Blanco, C.E.; Steinbusch, H.W.M.,""Impact of perinatal asphyxia on the GABAergic and locomotor system""Neuroscience2003pp. 83-96
Bibliographic PageFull Text - Hirst, Warren D.; Babbs, Adam J.; Green, Andrew; Minton, Jayne A.L.; Shaw, Tracy E.; Wise, Alan; Rice, Simon Q.; Pangalos, Menelas N.; Price, Gary W.,""Pharmacological characterisation of a cell line expressing GABAB1b and GABAB2 receptor subunits""Biochemical Pharmacology2003pp. 1103-1113
Bibliographic PageFull Text - Ahboucha, Samir; Desjardins, Paul; Chatauret, Nicolas; Pomier-Layrargues, Gilles; Butterworth, Roger F.,""Normal coupling of brain benzodiazepine and neurosteroid modulatory sites on the GABA-A receptor complex in human hepatic encephalopathy""Neurochemistry International2003pp. 551-556
Bibliographic PageFull Text - Frolund, Bente; Tagmose, Lena; Jorgensen, Anne T.; Kristiansen, Uffe; Stensbol, Tine B.; Liljefors, Tommy; Krogsgaard-Larsen, Povl,""Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists""European Journal of Medicinal Chemistry2003pp. 447-449
Bibliographic PageFull Text - Gould, Georgianna G.; Mehta, Ashok K.; Frazer, Alan; Ticku, Maharaj K.,""Quantitative autoradiographic analysis of the new radioligand [3H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([3H]NCS-382) at g-hydroxybutyric acid (GHB) binding sites in rat brain""Brain Research2003pp. 51-56
Bibliographic PageFull Text - Hamon, Alain; Morel, Alain; Hue, Bernard; Verleye, Marc; Gillardin, Jean-Marie,""The modulatory effects of the anxiolytic etifoxine on GABAA receptors are mediated by the b subunit""Neuropharmacology2003pp. 293-303
Bibliographic PageFull Text - Biggio, G.,""Molecular mechanisms of tolerance to and withdrawal of GABAA receptor modulators""European Neuropsychopharmacology2003pp. S2-S4
Bibliographic PageFull Text - Burt, David R.,""Reducing GABA Receptors""Life Sciences2003pp. 1741-1758
Bibliographic PageFull Text - Sienkiewicz-Jarosz, Helena; Szyndler, Janusz; Czlonkowska, Agnieszka I.; Siemiatkowski, Marek; Maciejak, Piotr; Wislowska, Aleksandra; Zienowicz, Malgorzata; Lehner, Malgorzata; Turzynska, Danuta; Bidzinski, Andrzej; Plaznik, Adam,""Rat behavior in two models of anxiety and brain [3H]muscimol binding: pharmacological, correlation, and multifactor analysis""Behavioural Brain Research2003pp. 17-22
Bibliographic PageFull Text - El Yacoubi, M.; Ledent, C.; Parmentier, M.; Costentin, J.; Vaugeois, J.-M.,""Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade""Neuropharmacology2003pp. 977-985
Bibliographic PageFull Text - Krehan, Dorte; Frolund, Bente; Ebert, Bjarke; Nielsen, Birgitte; Krogsgaard-Larsen, Povl; Johnston, Graham A. R.; Chebib, Mary,""Aza-THIP and related analogues of THIP as GABAC antagonists""Bioorganic and Medicinal Chemistry2003pp. 4891-4896
Bibliographic PageFull Text - Gower, Alma J.; Falter, Ursula; Lamberty, Yves,""Anxiolytic effects of the novel anti-epileptic drug levetiracetam in the elevated plus-maze test in the rat""European Journal of Pharmacology2003pp. 67-74
Bibliographic PageFull Text - Biggio, Giovanni; Dazzi, Laura; Biggio, Francesca; Mancuso, Luisa; Talani, Giuseppe; Busonero, Fabio; Mostallino, Maria Cristina; Sanna, Enrico; Follesa, Paolo,""Molecular mechanisms of tolerance to and withdrawal of GABAA receptor modulators""European Neuropsychopharmacology2003pp. 411-423
Bibliographic PageFull Text - Pericic, Danka; Strac, Dubravka Svob; Jembrek, Maja Jazvinscak; Rajcan, Ivana,""Prolonged exposure to g-aminobutyric acid up-regulates stably expressed recombinant a1b2g2s GABAA receptors""European Journal of Pharmacology2003pp. 117-125
Bibliographic PageFull Text - Clark, Ann S.; Henderson, Leslie P.,""Behavioral and physiological responses to anabolic-androgenic steroids""Neuroscience and Biobehavioral Reviews2003pp. 413-436
Bibliographic PageFull Text - Obradovic, Dragan I.; Savic, Miroslav M.; Andjelkovic, Draginja S.; Ugresic, Nenad D.; Bokonjic, Dubravko R.,""The influence of midazolam and flumazenil on rat brain slices oxygen consumption""Pharmacological Research2003pp. 127-131
Bibliographic PageFull Text - Mehta, Ashok K.; Ticku, Maharaj K.,""An investigation on the role of nitric oxide in the modulation of the binding characteristics of various radioligands of GABAA receptors by 5a-pregnan-3a-ol-20-one in the rat brain regions""Brain Research1999pp. 164-167
Bibliographic PageFull Text - Kang-Park, M.-H.; Wilson, W.A.; Moore, S.D.,""Differential actions of diazepam and zolpidem in basolateral and central amygdala nuclei""Neuropharmacology2004pp. 1-9
Bibliographic PageFull Text - Jobst, E.E.; Robinson, D.W.; Allen, C.N.,""Potential pathways for intercellular communication within the calbindin subnucleus of the hamster suprachiasmatic nucleus""Neuroscience2004pp. 87-99
Bibliographic PageFull Text - Caldji, Christian; Diorio, Josie; Meaney, Michael J.,""Variations in maternal care in infancy regulate the development of stress reactivity""Biological Psychiatry2000pp. 1164-1174
Bibliographic PageFull Text - Liu, Min; Glowa, John R.,""Regulation of benzodiazepine receptor binding and GABAA subunit mRNA expression by punishment and acute alprazolam administration""Brain Research2000pp. 23-33
Bibliographic PageFull Text - Pirker, S.; Schwarzer, C.; Wieselthaler, A.; Sieghart, W.; Sperk, G.,""GABAA receptors: immunocytochemical distribution of 13 subunits in the adult rat brain""Neuroscience2000pp. 815-850
Bibliographic PageFull Text - LaBuda, Christopher J.; Fuchs, Perry N.,""Aspirin attenuates the anxiolytic actions of ethanol""Alcohol2000pp. 287-290
Bibliographic PageFull Text - Herzog, Christopher D.; Gandhi, Chetan; Bhattacharya, Papia; Walsh, Thomas J.,""Effects of Intraseptal Zolpidem and Chlordiazepoxide on Spatial Working Memory and High-Affinity Choline Uptake in the Hippocampus""Neurobiology of Learning and Memory2000pp. 168-179
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