INTRASTRIATAL RO15-4513 FUNCTIONALLY ANTAGONIZES ETHANOL-INDUCED MOTOR INCOORDINATION AND STRIATAL ADENOSINERGIC MODULATION OF ETHANOL-INDUCED MOTOR INCOORDINATION IN RATS

To study the role of the striatum in modulating the effects of adenosi ne agonists and benzodiazepine inverse agonists on acute ethanol-induc ed motor impairment, we evaluated the effect of direct intrastriatal R o15-4513 [0.625, 1.25 and 2.5 ng], a partial inverse agonist of benzod iazepine receptor, on ethanol-induced motor incoordination. A signific ant and nearly dose-dependent antagonism by Ro15-4513 was observed, wh ich suggests involvement of the striatum in ethanol-induced motor inco ordination. No effect of IST Ro15-4513 on motor incoordination induced by Na-pentobarbital (10 mg/kg, i.p.) was noted, indicating the select ivity of the antiethanol action of Ro15-4513. The IST adenosine agonis t N-6-cyclohexyladenosine (CHA) markedly accentuated ethanol-induced m otor incoordination in a dose-related manner, suggesting a striatal ad enosinergic modulation of ethanol-induced motor incoordination. The IS T Ro15-4513 also significantly antagonized the accentuating effects of CHA on ethanol-induced motor incoordination. No change in normal moto r coordination was observed after IST CHA or Ro15-4513 when followed b y saline administration instead of ethanol. No accentuating effect by intrahippocampal CHA on ethanol-induced motor incoordination was seen, which suggests the selectivity of striatal adenosinergic modulation o f ethanol-induced motor incoordination. There was no significant radio activity present in the systemic circulation, in the CSF or in brain a reas other than striatum after intrastriatal [H-3]Ro15-4513 or [H-3]CH A and ethanol injection. Data obtained so far support the involvement of striatum in ethanol's ataxia as well as striatal adenosinergic modu lation of the central effect(s) of ethanol, possibly through Ro15-4513 -sensitive mechanism(s).