ANTAGONISM BY INTRACEREBELLAR RO15-4513 OF ACUTE ETHANOL-INDUCED MOTOR INCOORDINATION IN MICE

The possible antiethanol effect of intracerebellarly microinjected Ro15-4513 was investigated using motor incoordination as the test response. The results of this study further confirmed reports from this and other laboratories that this partially negative ligand of benzodiazepine selectively attenuated and nearly reversed the motor impairment of acute ethanol. The attenuation observed after microinjections of doses of 0.05, 0.1, and 0.5 ng was significant and dose related. There was no effect on normal coordination when the highest dose, 0.5 ng, was administered followed by saline instead of a test dose of ethanol. When 0.5 ng of Ro15-4513 alone was microinjected into the cerebellum, no significant change in the locomotor activity was observed. Even a 10-fold higher intracerebellar dose (5 ng) of Ro15-4513 administered alone produced no significant changes in locomotor activity. This suggests that attenuation of ethanol-induced motor incoordination was most likely due to the selective antiethanol effect of Ro15-4513 at the dose range used in the present investigation. The antiethanol effect of intracerebellar Ro15-4513 also reaffirmed the well-known belief that the cerebellum is an important brain region for ethanol's motor-impairing effect. The results also indirectly suggest the inhibition of GABA(A)-gated chloride ion channel activity as the most likely basis of Ro15-4513's antiethanol effect.