Pergamon PharmacologyBiochemistry and Behavior,Vol. 48, No. 4, pp. 1019-1024,1994 Copyright© 1994 Elsevier Science Ltd Primed in the USA.All rightsreserved 0091-3057/94$6.00 + .oo 0091-3057(94)E0016-B BRIEF COMMUNICATION Evidence for the Contribution of CCK B Receptor Mechanisms to Individual Differences in Amphetamine-Induced Locomotion G. A. HIGGINS,* T. L. SILLS,~ D. M. TOMKINS,* E. M. SELLERS*:~ AND F. J. VACCARINOt§ 1 *Addiction Research Foundation and Departments of Pharmacology, "fPsychology, ~4edicine, and §Psychiatry, University of Toronto, 100 St. George Street, Toronto, Ontario, Canada MSS 1A1 Received 26 July 1993 HIGGINS, G. A., T. L. SILLS, D. M. TOMKINS, E. M. SELLERS AND F. J. VACCARINO. Evidence for the con- tribution of CCKBreceptor mechanisms to individual differences in amphetamine-induced locomotion. PHARMACOL BIOCHEM BEHAV 48(4) 1019-1024, 1994.--Recent evidence shows that rats exhibit individual differences in their locomo- tor response to amphetamine (AMP). Moreover, evidence has accumulated showing that high-AMP responders exhibit more mesolimbic dopaminergic (DAergic) activation in response to AMP treatment than low-AMP responders. Cholecystokinin (CCK) is a peptide that is colocalised with mesolimbic DA and exerts complex modulatory actions on DA function. Two CCK receptor subtypes have been identified and selectiveantagonists have been developed. To examine the possible contribution of endogenous CCK mechanisms to individual differences in responsivity to AMP treatment, male Wistar rats were divided into low- and high-AMP responders based on a median split of their locomotor response to AMP and the effects of the selective CCK antagonists L365-260 (CCKB; 0.01, 0.1, 0.5 mg/kg; n = 16) and devazepide (CCK^; 0.001, 0.01, 0.1 mg/kg; n = 23) were determined. Results showed that L365-260(0.1 mg/kg) potentiated AMP-induced hyperactivity in low-AMP responders but did not affect AMP-induced hyperactivity in high-AMP responders. Devazepide was without effect in both groups of animals. This pattern of results suggests that CCKR, but not CCKA, receptor mechanisms contribute to interindividual variation in responsivity to AMP. Amphetamine Locomotion Cholecystokinin Antagonists Devazepide L365-260 Individual differences Rat THE peptide cholecystokinin (CCK) exerts important neuro- modulatory effects in both the CNS and periphery (47). Cur- rent research suggests that these effects are mediated via two distinct receptor subtypes, termed CCKA (alimentary) and CCKB (brain) (14,15,27). As the nomenclature suggests, it is the CCKA receptor that is the predominant form in the periph- ery, although there is a limited distribution of this subtype within the CNS 04,15). The CCKB receptor, on the other hand, is widely distributed throughout most brain regions of various mammalian species 04,15). Selective agonists and an- tagonists have been developed for both receptor subtypes, with perhaps the most widely used antagonists presently being the substituted benzodiazepines, devazepide (formerly MK329, L364-718) (3,7) and L365-260 (24), which show approximately one hundredfold selectivity for CCKA and CCKB receptors, respectively (3,7,15,24). Based on the observation that CCK and dopamine (DA) are colocalised within certain neurons comprising the A10 mesolimbic pathway (17,18,24,36,37), there has been exten- sive research examining the interaction between these neuro- transmitters at both the biochemical (1,9,25,42-44) and be- havioral (4-6,11,23,29,38,40,45,46) level. It has been shown ' Requests for reprints should be addressed to F. J. Vaccarino, Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ontario, Canada M5S IA1. 1019