Reversal of the anti-conflict action of valproate by various GABA and benzodiazepine antagonists.
The effects of RO 15-1788, RO 5-3663, picrotoxin and bicuculline on the anti-conflict properties of valproate were studied in rats using a modified Vogel 's conflict test procedure. A low dose of the benzodiazepine (BDZ) antagonist, RO 15-1788 (5 mg/kg), blocked the anti-punishment properties of valproate (400 mg/kg), whereas no antagonism was observed after a high dose (25 mg/kg) of the BDZ antagonist. High doses of RO 5-3663 or picrotoxin also reversed the anti-conflict action of valproate. Bicuculline did not change the effects of valproate in this test situation. The suppressive effect of valproate on locomotor activity was reversed by a low dose (5 mg/kg) of RO 15-1788, but not by the other antagonists. RO 5-3663 was the only antagonist which effectively reversed the muscle relaxant effects of valproate observed in a Rotarod performance test. These findings indicate that various pharmacological actions of valproate may be due to a complex interplay with several sites at the GABA-BDZ-receptor complex.
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001570:Benzodiazepinones / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003220:Conflict, Psychological; D005442:Flumazenil; D018756:GABA Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D014635:Valproic Acid / Q000494:pharmacology*
D001569:Benzodiazepines; D001570:Benzodiazepinones; D001640:Bicuculline; D005442:Flumazenil; D018756:GABA Antagonists; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D014635:Valproic Acid; C022193:Ro 5-3663