The effects of haloperidol on amphetamine- and methylphenidate-induced conditioned place preferences and locomotor activity.

Abstract

Place preferences induced by the indirect dopamine (DA) receptor agonists amphetamine (AMP) and methylphenidate (MPD) were investigated using an unbiased compartment procedure. In this procedure, prior to drug conditioning, rats did not exhibit preferences for either of the two compartments in a shuttle box. Both stimulants produced place preferences. Repeated testing of the MPD conditioned animals revealed an extinction-like decrease in preferences, suggesting that place preferences produced by MPD result from conditioning of MPD's reinforcing properties to environmental cues. During conditioning, the DA receptor antagonist haloperidol was administered prior to drug (S+) treatments, or prior to both drug and vehicle (S-) treatments. Haloperidol pretreatment blocked place preferences induced by AMP but not by MPD. In contrast, haloperidol blocked locomotor activity stimulated by either AMP or MPD. These results suggest that the reinforcing properties of MPD and AMP may be mediated by different mechanisms, while the locomotor stimulant effects of the two drugs have common neural substrates.