beta-Carbolines activate neurons in the substantia nigra pars reticulata: an effect reversed by diazepam and Ro15-1788.
Diazepam (0.5 mg/kg i.v.) was found to inhibit the firing rate of substantia nigra pars reticulata (SN-PR) cells by 50%. In contrast, beta-CCM, at the doses of 125 and 250 micrograms/kg i.v. increased the firing rate by 90 and 150%, respectively, while DMCM produced similar increases at doses of 250 and 500 micrograms/kg i.v. Both beta-carboline-induced excitation and diazepam-induced inhibition were reversed to baseline values by the specific antagonist of benzodiazepine recognition sites, Ro15-1788 (2.0 mg/kg i.v.). Moreover, the stimulant effect of beta-carbolines was also reversed by diazepam (1.0 mg/kg) to about 50% of baseline. The results indicate that beta-carbolines specifically influence the activity of SN-PR cells through a mechanism opposite to that of benzodiazepines themselves, acting on benzodiazepine recognition sites.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D005442:Flumazenil; D007211:Indoles / Q000037:antagonists & inhibitors*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D001570:Benzodiazepinones; D002243:Carbolines; D007211:Indoles; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam