Depression of cerebellar cGMP by barbiturates. Relationship to locomotor activity.
The intravenous administration of pentobarbital, phenobarbital or barbital produced a dose-related depression of the levels of cyclic guanosine monophosphate (cGMP) in the cerebellum of male Sprague-Dawley rats. This depression of cGMP occurred with doses of pentobarbital and barbital which did not reduce locomotor activity. Further, the time-course of the recovery of locomotor activity following the administration of an anesthetic dose of pentobarbital preceded that for the recovery of the levels cGMP in the cerebellum. In a separate study, pretreatment with picrotoxinin reversed the significant depression of cGMP in the cerebellum produced by the smallest dose of pentobarbital. Collectively, these data suggest that the effects of the barbiturates on cGMP in the cerebellum are not exclusively or predominantly the result of a drug-related depression of locomotor activity and may be, at least partially, mediated via a barbiturate-induced potentiation of a GABA receptor-mediated mechanism.
D000818:Animals; D001462:Barbital / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A
D001462:Barbital; D001463:Barbiturates; D000242:Cyclic AMP; D010424:Pentobarbital; D010634:Phenobarbital; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A