Pharmacology Biochemistry andBehavior, Vol.43, pp. 377-380, 1992 0091-3057/92$5.00 + .00 Printed in the U.S.A. All rights reserved. Copyright © 1992 PergamonPress Ltd. Pipradrol Conditioned Place Preference is Blocked by SCH23390 NORMAN M. WHITE 1 AND NOBORU HIROI 2 Department of Psychology, McGill University, Montreal, Quebec, Canada H3A 1B1 Received 15 July 1991 WHITE, N. M. AND N. HIROI. Pipradrol conditioned placepreference is blockedby SCH23390. PHARMACOL BIO- CHEM BEHAV 43(2) 377-380, 1992.--We investigated the effect of the selective Dl dopamine antagonist, SCH23390, on the establishment of a pipradrol-conditioned place preference (CPP). Among various doses of pipradrol (6.25-75.0 mg/kg, SC), a CPP was established at 25.0 mg/kg. SCH23390 (0.16 mg/kg, IP) blocked the establishment of a CPP by this dose of pipradrol. The results suggest that pipradrol produces a rewarding effect and that this effect may involve activation of Dmdopaminereceptors. SCH23390 Conditioned place preference Reinforcement Motivation Dopamine Dl Affect Reward Conditioned reward THE conditioned place preference (CPP) paradigm has been used to assess the affective properties of various drugs, includ- ing stimulants and opiates (7,13). Numerous studies have shown that these drugs produce robust CPPs, suggesting that they have rewarding properties. Other findings suggest that central dopamine systems are involved in the rewarding prop- erties of stimulants as revealed in the CPP paradigm. Amphet- amine establishes CPPs by releasing dopamine in the nucleus of accumbens, a terminal area of the mesolimbic dopamine pathway (8,9,33). The site of action of stimulants other than amphetamine is not well understood, and it is not clear if dopamine is involved in their CPP-establishing effects. Except at very high doses (20), the dopamine receptor antagonist, haloperidol, failed to block the establishment of a methylphenidate CPP (21). Martin-Iverson et al. (20) have also reported that 6- hydroxydopamine (6-OHDA) lesions, which depleted 81070 of striatal dopamine and 7007o of accumbens dopamine, were ineffective in blocking the establishment of a methylphenidate CPP. This finding must be interpreted cautiously because it is known that more than 90°70 depletion is required to abolish both dopamine release (29,39) and its behavioral effect when it is released from the reserpine-sensitive pool (16). Neverthe- less, these findings raise the question of whether or not meth- ylphenidate, a non-amphetamine-type stimulant, may estab- lish CPPs by acting on neurotransmitter system(s) other than dopamine. The nonamphetamine stimulants (pipradrol and methyl- phenidate) release dopamine from the reserpine-sensitive do- pamine pool (6,12,30). Depletion of the reserpine-sensitive do- pamine pool after CPP training with amphetamine, but before testing in the absence of the drug, blocks expression of the CPP, suggesting that dopamine in the reserpine-sensitive pool may mediate the effects of conditioned rewarding stimuli on behavior in the CPP paradigm (13,16). We have also reported that the effects of conditioned rewarding stimuli (in the am- phetamine CPP paradigm) are preferentially blocked by the D~ dopamine antagonist, SCH23390, as compared to D 2 dopa- mine antagonists (13,17). These f'mdings suggest the possibility that the reserpine- sensitive dopamine pool is functionally linked to the D~ dopa- mine receptor. To test this hypothesis, as well as to examine the question of the nature of the CPP produced by the nonam- phetamine stimulant, pipradrol, we studied the effect of the Dl-selective dopamine antagonist, SCI-I23390, on the estab- lishment of a CPP by pipradrol. The initial doses of pipradrol used were those previously shown by Robbins (26-28) to affect conditioned reward. When these doses proved ineffective, higher doses were used. METHOD Subjects Subjects were 56 experimentally naive, male Long-Evans rats purchased from Charles River Canada (St. Constant, Quebec) weighing 275-310 g at the start of the experiments. Animals were individually housed with food and water avail- able ad lib. i Requests for reprints should be addressed to Norman M. White, Department of Psychology, McGill University, 1205 Dr. Penfield Avenue, Montreal, Quebec H3A IBI Canada. 2 Current address: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, E-25-618, Cambridge, MA 02139. 377