Haloperidol prevents ethanol-stimulated locomotor activity but fails to block sensitization

The effect of the dopamine receptor antagonist haloperidol on the development of sensitization to ethanol-induced increases in locomotor activity was examined in DBA/2J mice. In Experiment 1, different groups of mice were given saline or ethanol (2 g/kg) immediately before each of four locomotor activity sessions (48-h intervals), and 1 h after pretreatment with saline, 0.10 or 0.15 mg/kg haloperidol. During a subsequent test, mice showed locomotor sensitization despite blockade of ethanol stimulated activity by haloperidol on the first conditioning trial. Moreover, test session activity was reduced in subjects that had previously received haloperidol, even though haloperidol was not present during testing. The second experiment examined the nature of the latter finding by comparing subjects that received equal exposure to haloperidol but differed in the pairing of its administration with the activity chambers. After four conditioning trials, each group was tested in the absence of haloperidol. Mice that had previously received haloperidol paired with the activity chambers were less active than control groups, suggesting development of a conditioned suppression of activity. Overall, these results suggest a dissociation of the neurobiological mechanisms that mediate the acute locomotor stimulant effects of ethanol and those mediating sensitization. Further, these studies illustrate the importance of antagonist-alone control groups that assess the possible influence of associative learning induced by the antagonist itself.