The action of benzodiazepine antagonist Ro 15-1788 on the effects of GABA-ergic drugs.
The interaction of Ro 15-1788 (5 mg kg-1 i.p.) a benzodiazepine antagonist, with GABA-ergic drugs muscimol (1.4 mg kg-1 i.p.), fenibut (100 mg kg-1 i.p.) and baclofen (5 mg kg-1 i.p.) was examined in behavioural and biochemical studies in rats. All the above-mentioned GABA-ergic drugs produced motor depression and with the exception of muscimol, where anti-aggressive effect was evident, fenibut and baclofen showed only slight antiaggresive properties. Ro 15-1788 attenuated the motor depression produced by these compounds but potentiated their antiaggressive effect. Moreover, it was found that Ro 15-1788 itself possessed dose-related antiaggressive properties. Fenibut increased, whereas muscimol and Ro 15-1788 decreased, the GABA content in the rat striatum. Ro 15-1788 and all the studied GABA-ergic compounds increased the level of the dopamine metabolite 3,4-dihyroxyphenylacetic acid (DOPAC) in the striatum. In spite of this no further increase of DOPAC was observed after concomitant use of Ro 15-1788 with GABA-ergic drugs. The action of investigated GABA-ergic drugs via GABA receptors linked to benzodiazepine receptors is suggested.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001570:Benzodiazepinones / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D005442:Flumazenil; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D001570:Benzodiazepinones; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D015102:3,4-Dihydroxyphenylacetic Acid; D001569:Benzodiazepines; D009118:Muscimol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D001418:Baclofen