The action of benzodiazepine antagonist Ro 15-1788 on the effects of GABA-ergic drugs
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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 antiagressive 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 antiagressive 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 dopaminc metabolite 3,4-dihydroxyphenylacetic 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.
Key wordsBenzodiazepine antagonist Ro 15-1788 GABA-ergic drugs Interaction
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