title: Rats with different thresholds for DMCM-induced clonic convulsions differ in the sleep-time of diazepam and [(3)H]-Ro 15-4513 binding.
abstract: The current study investigated the possible inherent relationship between convulsions and sleep involving the GABA(A)/benzodiazepine site complex. The aim of this study was to determine if rats with high (HTR) and low (LTR) thresholds for clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ in the following aspects: (1) sensitivity to the hypnotic effects of the GABA(A) positive allosteric modulators diazepam, pentobarbital and ethanol and (2) in the binding of [(3)H]-flunitrazepam, a benzodiazepine agonist, measured by autoradiography, and [(3)H]-Ro 15-4513, a benzodiazepine partial inverse agonist, to membranes from discrete brain regions. The LTR subgroup presented a shorter diazepam-induced sleeping time compared to that of the HTR subgroup. Biochemical assays revealed that the LTR subgroup did not differ in [(3)H]-flunitrazepam binding compared to the HTR subgroup. With respect to the binding of [(3)H]-Ro 15-4513, the LTR subgroup had higher binding in the brainstem and lower binding in the striatum compared to the HTR subgroup. These results suggest that differences in the benzodiazepine site on the GABA(A) receptor may underlie the susceptibility to DMCM-induced convulsions and sensitivity to the hypnotic effect of diazepam.
authors: Departamento de Psicobiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Botucatu 862, 1 Andar, Vila Clementino, São Paulo, SP 04023-900, Brazil. marcosbc@psicobio.epm.br
authors: Marcos Brandão
authors: MB
authors: Contó
authors: Débora Cristina
authors: DC
authors: Hipólide
authors: José Gilberto Barbosa
authors: JG
authors: de Carvalho
authors: Marco Antonio Campana
authors: MA
authors: Venditti
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001345:Autoradiography; D001386:Azides / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D002243:Carbolines / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity*; D003975:Diazepam / Q000627:therapeutic use*; D004056:Differential Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005445:Flunitrazepam / Q000493:pharmacokinetics; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D001386:Azides; D002243:Carbolines; D003292:Convulsants; D018757:GABA Modulators; D014316:Tritium; D001569:Benzodiazepines; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D000431:Ethanol; D005445:Flunitrazepam; C042957:Ro 15-4513; D010424:Pentobarbital; D003975:Diazepam