To study the role of the striatum in modulating the effects of
adenosine agonists and
benzodiazepine inverse agonists on acute
ethanol-induced motor impairment, we evaluated the effect of direct intrastriatal
Ro15-4513 [0.625, 1.25 and 2.5 ng], a partial inverse agonist of
benzodiazepine receptor, on
ethanol-induced motor
incoordination. A significant and nearly dose-dependent antagonism by
Ro15-4513 was observed, which suggests involvement of the striatum in
ethanol-induced motor
incoordination. No effect of IST
Ro15-4513 on motor
incoordination induced by Na-
pentobarbital (10 mg/kg, i.p.) was noted, indicating the selectivity of the antiethanol action of
Ro15-4513. The IST
adenosine agonist
N6-cyclohexyladenosine (CHA) markedly accentuated
ethanol-induced motor
incoordination in a dose-related manner, suggesting a striatal adenosinergic modulation of
ethanol-induced motor
incoordination. The IST
Ro15-4513 also significantly antagonized the accentuating effects of CHA on
ethanol-induced motor
incoordination. No change in normal motor coordination was observed after IST CHA or
Ro15-4513 when followed by 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 of
ethanol-induced motor
incoordination. There was no significant radioactivity present in the systemic circulation, in the CSF or in brain areas other than striatum after intrastriatal [3H]Ro15-4513 or [3H]CHA and
ethanol injection. Data obtained so far support the involvement of striatum in
ethanol's
ataxia as well as striatal adenosinergic modulation of the central effect(s) of
ethanol, possibly through Ro15-4513-sensitive mechanism(s).