EVIDENCE FOR THE INVOLVEMENT OF DOPAMINE-RECEPTORS IN ETHANOL-INDUCEDHYPERACTIVITY IN MICE

Based on the hypothesis that drugs of abuse increase locomotor activit y through mechanisms related to reinforcement, i.e. the mesolimbic dop amine (DA) system, ethanol-induced hyperactivity might provide a scree ning model to investigate the effect of ethanol on reward pathways. In the present study, ethanol had bidirectional effects on locomotion in mice: hyperactivity at low doses (2-3 g/kg) and sedation at high dose s (4-5 g/kg). Such high doses induced a loss of righting reflex (LRR). The stimulant effect of ethanol was blocked by the D-2/D-3 antagonist s, haloperidol (0.2 mg/kg) and tiapride (30-60 mg/kg), and by the D-1 antagonist, SCH 23390 (0.03 mg/kg) whereas the non selective DA antago nist, clozapine decreased ethanol-induced hyperactivity at a dose (1 m g/kg) which also decreased activity in control animals. Unlike haloper idol and clozapine which potentiated LRR induced by ethanol, the selec tive DA antagonists, tiapride and SCH 23390, had no effect. Pretreatme nt with the D-2/D-3 agonist, quinpirole (0.1-0.3 mg/kg), reduced hyper activity induced by ethanol presumably by stimulation of pre-synaptic receptors but did not change LRR. The D-1 full agonist, SKF 81297 whic h produced hyperactivity by itself and the D-1 partial agonist, SKF 38 393, did not specifically affect ethanol-induced activities. The resul ts indicate that activation of D-1 and D-2/D-3 DA receptors is implica ted in ethanol-induced hyperactivity whereas other mechanisms might me diate the sedative effects of ethanol. Tiapride and haloperidol, both used in the management of alcohol dependence, might exert beneficial e ffects by counteracting the reinforcing effects of ethanol. Tiapride's lack of interaction with the depressant effects of ethanol may accoun t for its better tolerance in alcoholic patients. (C) 1997 Elsevier Sc ience Ltd.