GABAA receptor subtypes: Therapeutic potential in down syndrome, affective disorders, schizophrenia, and autism

Annual Review of Pharmacology and Toxicology

Volumn 54, Issue , 2014, Pages 483-507

  Rudolph, Uwe ^a   Möhler, Hanns ^b,c  

^a MCLEAN HOSPITAL   (United States)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c ETH ZURICH   (Switzerland)

Author keywords

Anxiolytics; Autism; Cognition enhancer; Depression; Down syndrome; Schizophrenia

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA2; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA3; 4 AMINOBUTYRIC ACID A RECEPTOR ALPHA5; 4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; ANXIOLYTIC AGENT; MRK 409; NEUROSTEROID; OCINAPLON; PENTETRAZOLE; RO 4938581; TPA 023; UNCLASSIFIED DRUG;

AMNESIA; AMYGDALOID NUCLEUS; ANXIETY; ANXIETY DISORDER; AUTISM; COGNITION; COGNITIVE DEFECT; COGNITIVE THERAPY; DEPENDENT PERSONALITY DISORDER; DEPRESSION; DOWN SYNDROME; EMOTION; FEAR; GENE TARGETING; HUMAN; LINGUISTICS; MEMORY; MOOD DISORDER; NONHUMAN; OSCILLATION; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; TRANQUILIZING ACTIVITY; ANIMAL; BRAIN; CLINICAL TRIAL (TOPIC); DISEASE MODEL; METABOLISM; MOLECULARLY TARGETED THERAPY; PHYSIOLOGY;

ANIMALS; AUTISTIC DISORDER; BRAIN; CLINICAL TRIALS AS TOPIC; COGNITION; DISEASE MODELS, ANIMAL; DOWN SYNDROME; HUMANS; MEMORY; MOLECULAR TARGETED THERAPY; MOOD DISORDERS; RECEPTORS, GABA-A; SCHIZOPHRENIA;

EID: 84891857314     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-011613-135947     Document Type: Review

References (149)

1. Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, et al. 2012. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat. Rev. Drug Discov. 11:141-68
2. Buzsáki G, Draguhn A. 2004. Neuronal oscillations in cortical networks. Science 304:1926-29
3. Klausberger T, Somogyi P. 2008. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321:53-57
4. Buzsáki G, Wang X-J. 2012. Mechanisms of gamma oscillations. Annu. Rev. Neurosci. 35:203-25 4a. Panzanelli P, Gunn BG, Schlatter MC, Benke D, Tyagarajan SK, et al. 2011. Distinct molecular mechanisms regulate GABAA receptor and gephyrin clustering at perisomatic and axo-axonic synapses on CA1 pyramidal cells. J. Physiol. 589:4959-80
5. Eccles JC. 1977. The Understanding of the Brain. New York: McGraw-Hill. 2nd ed.
6. Mann EO, Mody I. 2010. Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons. Nat. Neurosci. 13:205-12
7. A receptors: their function in the CNS and implications for disease. Neuron 73:23-34
8. A receptor α5 subunit-deficient mice. J. Neurophysiol. 95:2796-807
9. A receptors mediate phasic and tonic forms of inhibition in hippocampal pyramidal neurons. J. Neurophysiol. 96:846-57
10. A receptor-mediated tonic inhibition in rat somatosensory cortex. Cereb. Cortex 17:1782-87
11. A receptors. J. Neurochem. 102:1-12
12. Fritschy JM, Brünig I. 2003. Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications. Pharmacol. Ther. 98:299-323
13. A receptor subunits are necessary for tonic inhibition in the hippocampus? J. Neurosci. 28:1421-26
14. A receptor activity sets the threshold for long-term potentiation and constrains hippocampus-dependent memory. J. Neurosci. 30:5269-82
15. Ali AB, Thomson AM. 2008. Synaptic α5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex. Cereb. Cortex 18:1260-71
16. A receptors affect the dynamic range of mouse hippocampal kainate-induced gamma frequency oscillations in vitro. J. Physiol. 559:721-28
17. Glykys J, Mody I. 2007. Activation of GABAA receptors: views from outside the synaptic cleft. Neuron 56:763-70
18. Yee BK, Hauser J, Dolgov VV, Keist R, Möhler H, et al. 2004. GABA receptors containing the α5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear. Eur. J. Neurosci. 20:1928-36
19. A receptor α5 subunits disrupts the memory for location of objects in mice. Genes Brain Behav. 9:478-88
20. A receptors. Proc. Natl. Acad. Sci. USA 99:8980-85
21. A receptor. J. Neurosci. 22:5572-80
22. Möhler H. 2011. The rise of a new GABA pharmacology. Neuropharmacology 60:1042-49
23. A receptors which contain the alpha-5 subunit, in the elevated plus-maze test. Prog. Neuropsychopharmacol. Biol. Psychiatry 26:1389-92
24. A receptor subtype-selective modulators: II. α5-selective inverse agonists for cognition enhancement. Curr. Top. Med. Chem. 11:1203-14
25. A receptors alters alcohol drinking by rhesus monkeys. Alcohol Clin. Exp. Res. 37:624-34
26. A α5 receptors with cognition enhancing properties. J. Med. Chem. 47:5829-32
27. A receptors enhances cognition. J. Pharmacol. Exp. Ther. 316:1335-45
28. A receptor α5 subtype-selective inverse agonist α5IA. Pharmacol. Ther. 125:11-26
29. Nutt DJ, Besson M, Wilson SJ, Dawson GR, Lingford-Hughes AR. 2007. Blockade of alcohol's amnestic activity in humans by anα5 subtype benzodiazepine receptor inverse agonist. Neuropharmacology 53:810-20
30. A α5 subunit-containing receptors. Psychopharmacology 202:207-23
31. A α5 inverse agonists for the treatment of cognitive dysfunction. Bioorg. Med. Chem. Lett. 19:5940-44
32. A α5 receptors by RO4938581 attenuates discrete subchronic and early postnatal phencyclidine (PCP)-induced cognition deficits in rats. Psychopharmacology 221:451-68
33. Ferrarelli F, Massimini M, Peterson MJ, Riedner BA, Lazar M, et al. 2008. Reduced evoked gamma oscillations in the frontal cortex in schizophrenia patients: aTMS/EEG study. Am. J. Psychiatry 165:996-1005
34. Martin LJ, Oh GH, Orser BA. 2009. Etomidate targetsα5 gamma-aminobutyric acid subtype Areceptors to regulate synaptic plasticity and memory blockade. Anesthesiology 111:1025-35
35. A receptors. Cell Rep. 2:488-96
36. A receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J. Neurosci. 26:3713-20
37. Rudolph U, Antkowiak B. 2004. Molecular and neuronal substrates for general anesthetics. Nat. Rev. Neurosci. 5:709-20
38. A/BzR subtypes (α1β3γ2, α5β3γ2, and α6β3γ2) via a comprehensive ligand-mapping approach. J. Med. Chem. 43:71-95
39. 3H]RY 80: a high-affinity, selective ligand for γ-aminobutyric acidA receptors containing alpha-5 subunits. JPET 283:488-93
40. Fischer BD, Licata SC, Edwankar RV, Wang ZJ, Hung S, et al. 2010. Anxiolytic-like effects of 8-acetylene imidazobenzodiazepines in a rhesus monkey conflict procedure. Neuropharmacology 59:612-18
41. A receptors promotes action potential firing of neocortical neurons during up-states. Eur. J. Pharmacol. 703:18-24
42. Lingford-Hughes A, Hume SP, Feeney A, Hirani E, Osman S, et al. 2002. Imaging the GABAbenzodiazepine receptor subtype containing the α5-subunit in vivo with [11C]Ro15 4513 positron emission tomography. J. Cereb. Blood Flow Metab. 22:878-89
43. Lee JL. 2010. Memory reconsolidation mediates the updating of hippocampus memory content. Front. Behav. Neurosci. 4:168
44. McKenzie S, Eichenbaum H. 2011. Consolidation and reconsolidation: two lives of memories? Neuron 71:224-33
45. Kaplan GB, Moore KA. 2011. The use of cognitive enhancers in animal models of fear extinction. Pharmacol. Biochem. Behav. 99:217-28
46. Davis M, Myers KM, Chhatwal J, Ressler KJ. 2006. Pharmacological treatments that facilitate extinction of fear: relevance to psychotherapy. NeuroRX 3:82-96
47. Chakrabarti L, Best TK, Cramer NP, Carney RS, Isaac JT, et al. 2010. Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat. Neurosci. 13:927-34
48. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, et al. 2010. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res. A Clin. Mol. Teratol. 88:1008-16
49. Gardiner K, Herault Y, Lott IT, Antonarakis SE, Reeves RH, Dierssen M. 2010. Down syndrome: from understanding the neurobiology to therapy. J. Neurosci. 30:14943-45
50. Lott IT, Dierssen M. 2010. Cognitive deficits and associated neurological complications in individuals with Down's syndrome. Lancet Neurol. 9:623-33
51. Liu C, Belichenko PV, Zhang L, Fu D, Kleschevnikov AM, et al. 2011. Mouse models for Down syndrome-associated developmental cognitive disabilities. Dev. Neurosci. 33:404-13
52. Siarey RJ, Stoll J, Rapoport SI, Galdzicki Z. 1997. Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down Syndrome. Neuropharmacology 36:1549-54
53. Siarey RJ, Carlson EJ, Epstein CJ, Balbo A, Rapoport SI, Galdzicki Z. 1999. Increased synaptic depression in the Ts65Dnmouse, amodel for mental retardation in Down syndrome. Neuropharmacology 38:1917-20
54. Kleschevnikov AM, Belichenko PV, Villar AJ, Epstein CJ, Malenka RC, Mobley WC. 2004. Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of Down syndrome. J. Neurosci. 24:8153-60
55. Fernandez F, Morishita W, Zuniga E, Nguyen J, Blank M, et al. 2007. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Nat. Neurosci. 10:411-13
56. A α5 receptormediated inhibition rescues functional and neuromorphological deficits in a mouse model of Down syndrome. J. Neurosci. 33:3953-66
57. A and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. Neurobiol. Dis. 45:683-91
58. McGaugh JL. 1966. Time-dependent processes in memory storage. Science 153:1351-58
59. Rueda N, Florez J, Martinez-Cue C. 2008. Chronic pentylenetetrazole but not donepezil treatment rescues spatial cognition in Ts65Dn mice, a model for Down syndrome. Neurosci. Lett. 433:22-27
60. A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice. J. Psychopharmacol. 25:1030-42
61. A α5-selective inverse agonist increases immediate early genes expression during memory processing in mice and rectifies their expression levels in a Down syndrome mouse model. Adv. Pharmacol. Sci. 2011:153218
62. Möhler H. 2012. Cognitive enhancement by pharmacological and behavioral interventions: the murine Down syndrome model. Biochem. Pharmacol. 84:994-99
63. Mégarbané A, Ravel A, Mircher C, Sturtz F, Grattan Y, et al. 2009. The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet. Med. 11:611-16
64. Kleschevnikov AM, Belichenko PV, Salehi A, Wu C. 2012. Discoveries in Down syndrome: moving basic science to clinical care. Prog. Brain Res. 197:199-221
65. Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, et al. 2005. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J. Psychopharmacol. 19:567-96
66. A receptor subtype functions. Curr. Opin. Pharmacol. 6:18-23
67. A receptor subtypes. Nat. Rev. Drug Discov. 10:685-97
68. Rudolph U, Crestani F, Benke D, Brünig I, Benson J, et al. 1999. Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes. Nature 401:796-800
69. A receptor α1 subtype. Nat. Neurosci. 3:587-92
70. A receptor mutant mouse studies. Nat. Neurosci. 3:1059
71. Löw K, Crestani F, Keist R, Benke D, Brünig I, et al. 2000. Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290:131-34
72. A receptor subtypes in mice. Neuropharmacology 63:250-58
73. A receptor subtypes mediate the anxiolytic properties of benzodiazepine site ligands in the conditioned emotional response paradigm. Eur. J. Neurosci. 23:2495-504
74. A receptors in mediating the anxiolytic effects of benzodiazepines. J. Neurosci. 25:10682-88
75. Facklam M, Schoch P, Bonetti EP, Jenck F, Martin JR, et al. 1992. Relationship between benzodiazepine receptor occupancy and functional effects in vivo of four ligands of differing intrinsic efficacies. J. Pharm. Exp. Ther. 261:1113-21
76. A receptors. J. Neurosci. 32:8611-19
77. LeDoux JE. 2007. The amygdala. Curr. Biol. 17:R868-74
78. Haubensak W, Kunwar PS, Cai H, Ciocchi S, Wall NR, et al. 2010. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468:270-76
79. Johansen JP, Cain CK, Ostroff LE, LeDoux JE. 2011. Molecular mechanisms of fear learning and memory. Cell 147:509-24
80. A receptor subtypes in the amygdala. Eur. J. Neurosci. 20:1281-89
81. Ehrlich I, Humeau Y, Grenier F, Ciocchi S, Herry C, Lüthi A. 2009. Amygdala inhibitory circuits and the control of fear memory. Neuron 62:757-71
82. A receptor modulates fear learning and plasticity in the lateral amygdala. Front. Behav. Neurosci. 3:37
83. A-associated genes in the amygdala after the acquisition and extinction of Pavlovian fear. Eur. J. Neurosci. 26:3631-44
84. Herry C, Ferraguti F, Singewald N, Letzkus JJ, Ehrlich I, Lüthi A. 2010. Neuronal circuits of fear extinction. Eur. J. Neurosci. 31:599-612
85. Bishop SJ. 2007 Neurocognitive mechanism of anxiety: an integrative account. Trends Cogn. Sci. 11:307-16
86. Rangel A, Hare T. 2010. Neural computations associated with goal-directed choice. Curr. Opin. Neurobiol. 20:262-70
87. Amemori K-I, Graybiel AM. 2012. Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making. Nat. Neurosci. 15:776-85
88. Larkum ME. 2013. The yin and yang of cortical layer 1. Nat. Neurosci. 16:114-15
89. Ressler KJ, Mayberg HS. 2007. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat. Neurosci. 10:1116-24
90. Lüscher B, Shen Q, Sahir N. 2011. The GABAergic deficit hypothesis ofmajor depressive disorder. Mol. Psychiatry 16:383-406
91. A receptor subtype selectivity to abuse liability and dependence potential of pharmacological treatments for anxiety and sleep disorders. CNS Spectrums 10:31-39
92. A receptor modulation and beyond. Pharmacol. Biochem. Behav. 90:74-89
93. A modulator for spasticity and neuropathic pain. Presented at Neuroscience 2011, Nov. 12-16, Washington, DC. Program 338.05, Poster C42
94. Concert Pharm. 2013. Concert Pharmaceuticals initiates Phase 1 clinical trial of CTP-354, a potential treatment for spasticity and pain. News Release, June 10
95. A/benzodiazepine ligands via selective partial agonist efficacy at α1 and α2/3 subtypes. J. Pharmacol. Exp. Ther. 332:4-16
96. A receptors, is a non-sedating anxiolytic in rodents and primates. J. Pharm. Exp. Ther. 316:410-22
97. A receptor modulation yields a novel pharmacological profile: the design and development of TPA023. Adv. Pharmacol. 57:137-85
98. A receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans. J. Psychopharmacol. 25:314-28
99. A receptor α subunits differentially contribute to diazepam tolerance after chronic treatment. PLoS ONE 7:e43054
100. A α2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers. J. Psychopharmacol. 22:24-32
101. A receptor α2/α3 subtype-selective partial agonist. J. Psychopharmacol. 25:329-44
102. A receptor modulator. Proc. Natl. Acad. Sci. USA 102:7380-85
103. Skolnick P. 2012. Anxioselective anxiolytics: on a quest for the holy grail. Trends Pharmacol. Sci. 33:611-20
104. Czobor P, Skolnick P, Beer B, Lippa A. 2010. A multicenter, placebo-controlled, double-blind, randomized study of efficacy and safety of ocinaplon (DOV 273,547) in generalized anxiety disorder. CNS Neurosci. Ther. 16:63-75
105. A receptor. Nat. Rev. Neurosci. 6:565-75
106. Rupprecht R, Papadopoulos V, Rammes G, Baghai T, Fan J, et al. 2010. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat. Rev. Drug Discov. 9:971-88
107. A receptors: molecular determinants and significance in health and disease. Neurochem. Int. 52:588-95
108. Rupprecht R, Rammes G, Eser D, Baghai T, Schüle C, et al. 2009. Translocator protein (18 kDa) as target for anxiolytics without benzodiazepine-like side effects. Science 325:490-93
109. Owen DR, Rupprecht R, Nutt DJ. 2013. Stratified medicine in psychiatry: a worrying example or new opportunity in the treatment of anxiety? J. Psychopharmacol. 27:119-22
110. Tan KR, Brown M, Laboùebe G, Yvon C, Creton C, et al. 2010. Neural bases for addictive properties of benzodiazepines. Nature 463:769-74
111. A) receptor subtypes in acute benzodiazepine physical dependencelike effects: evidence from squirrel monkeys responding under a schedule of food presentation. Psychopharmacology 227:347-54
112. Straub CJ, Carlezon WA Jr, Rudolph U. 2010. Diazepam and cocaine potentiate brain stimulation reward in C57BL/6J mice. Behav. Brain Res. 206:17-20
113. A receptor subtypes in benzodiazepine- induced enhancement of brain-stimulation reward. Neuropsychopharmacology 37:2531-40
114. A receptor modulators as hypnotics. J. Psychopharmacol. 24:1601-12
115. Najib JS. 2010. Efficacy and safety of zopiclone and eszopiclone in the treatment of primary and comorbid insomnia. In GABA and Sleep:Molecular, Functional and Clinical Aspects, ed. JM Monti, SR Pandi-Perumal, H Möhler, pp. 413-51. Basel, Switz.: Springer Basel AG
116. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. 2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:593-602
117. Holtzheimer PE, Mayberg HS. 2011. Stuck in a rut: rethinking depression and its treatment. Trends Neurosci. 34:1-9
118. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, et al. 1999. Reduced cortical gammaaminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch. Gen. Psychiatry 56:1043-47
119. Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, et al. 2004. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch. Gen. Psychiatry 61:705-13
120. Earnheart JC, Schweizer C, Crestani F, Iwasato T, Itohara S, et al. 2007. GABAergic control of adult hippocampal neurogenesis in relation to behavior indicative of trait anxiety and depression states. J. Neurosci. 27:3845-54
121. A-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat. Neurosci. 2:833-39
122. Shen Q, Lal R, Luellen BA, Earnheart JC, Andrews AM, Lüscher B. 2010. γ-Aminobutyric acid-type A receptor deficits cause hypothalamic-pituitary-adrenal axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biol. Psychiatry 68:512-20
123. A-receptor γ2 subunit. J. Neurosci. 33:15567-77
124. Gunther U, Benson J, Benke D, Fritschy JM, Reyes G, et al. 1995. Benzodiazepine-insensitive mice generated by targeted disruption of the γ2 subunit gene of γ-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. USA 92:7749-53
125. A receptors. Behav. Brain Res. 217:77-80
126. Carlezon WA Jr, Chartoff EH. 2007. Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat. Protoc. 2:2987-95
127. Nestler EJ, Hyman SE. 2010. Animal models of neuropsychiatric disorders. Nat. Neurosci. 13:1161-69
128. Amsterdam JD, Kaplan M, Potter L, Bloom L, Rickels K. 1986. Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacology 88:484-88
129. Petty F, Trivedi MH, Fulton M, Rush AJ. 1995. Benzodiazepines as antidepressants: Does GABA play a role in depression? Biol. Psychiatry 38:578-91
130. Fava M, McCall WV, Krystal A, Wessel T, Rubens R, et al. 2006. Eszopiclone co-administered with fluoxetine in patientswith insomnia coexisting with major depressive disorder. Biol. Psychiatry 59:1052-60
131. Brown RW, Noel DM, Smith JJ, Smith ML, Huggins KN, et al. 2011. Eszopiclone facilitation of the antidepressant efficacy of fluoxetine using a social defeat stress model. Pharmacol. Biochem. Behav. 99:648-58
132. Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, et al. 2005. GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. Psychopharmacology 180:191-205
133. Lewis DA, Hashimoto T, Volk DW. 2005. Cortical inhibitory neurons and schizophrenia. Nat. Rev. Neurosci. 6:312-24
134. Aα2/3 agonist TPA023. Biol. Psychiatry 67:998-1001
135. Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, et al. 2008. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am. J. Psychiatry 165:1585-93
136. Buchanan RW, Keefe RS, Lieberman JA, Barch DM, Csernansky JG, et al. 2011. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol. Psychiatry 69:442-49
137. A receptors to a dopamine hyperfunction. Proc. Natl. Acad. Sci. USA 102:17154-59
138. A receptors modulate the expression of prepulse inhibition. Mol. Psychiatry 10:201-7
139. A receptors are involved in the development of the latent inhibition effect. Neurobiol. Learn. Mem. 89:87-94
140. AR-positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia. Neuropsychopharmacology 36:1903-11
141. Delini-Stula A, Berdah-Tordjman D. 1996. Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia-a study group report. J. Psychiatr. Res. 30:239-50
142. Rubenstein JL, Merzenich MM. 2003. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav. 2:255-67
143. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, et al. 2011. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171-78
144. Gogolla N, LeBlanc JL, Quast KB, Südhof TC, Fagiolini M, Hensch TK. 2009. Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J. Neurodev. Disord. 1:172-181
145. Penagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, et al. 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147:235-46
146. Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, et al. 2010. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468:263-69
147. +/- mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489:385-90
148. BR1 receptors are altered in brains from subjects with autism. J. Autism Dev. Disord. 40:743-50
149. 11C]Ro15-4513 positron emission tomography study. Neuropharmacology 68:195-201