HALOPERIDOL PREVENTS ETHANOL-STIMULATED LOCOMOTOR-ACTIVITY BUT FAILS TO BLOCK SENSITIZATION

The effect of the dopamine receptor antagonist haloperidol on the deve lopment of sensitization to ethanol-induced increases in locomotor act ivity was examined in DBA/2J mice. In Experiment 1, different groups o f mice were given saline or ethanol (2 g/kg) immediately before each o f four locomotor activity sessions (48-h intervals), and 1 h after pre treatment with saline, 0.10 or 0.15 mg/kg haloperidol. During a subseq uent test, mice showed locomotor sensitization despite blockade of eth anol stimulated activity by haloperidol on the first conditioning tria l. Moreover, test session activity was reduced in subjects that had pr eviously received haloperidol, even though haloperidol was not present during testing. The second experiment examined the nature of the latt er finding by comparing subjects that received equal exposure to halop eridol but differed in the pairing of its administration with the acti vity chambers. After four conditioning trials, each group was tested i n the absence of haloperidol. Mice that had previously received halope ridol paired with the activity chambers were less active than control groups, suggesting development of a conditioned suppression of activit y. Overall, these results suggest a dissociation of the neurobiologica l mechanisms that mediate the acute locomotor stimulant effects of eth anol and those mediating sensitization. Further, these studies illustr ate the importance of antagonist-alone control groups that assess the possible influence of associative learning induced by the antagonist i tself.