EVIDENCE FOR THE CONTRIBUTION OF CCKB RECEPTOR MECHANISMS TO INDIVIDUAL-DIFFERENCES IN AMPHETAMINE-INDUCED LOCOMOTION

Recent evidence shows that rats exhibit individual differences in thei r locomotor response to amphetamine (AMP). Moreover, evidence has accu mulated showing that high-AMP responders exhibit more mesolimbic dopam inergic (DAergic) activation in response to AMP treatment than low-AMP responders. Cholecystokinin (CCK) is a peptide that is colocalised wi th mesolimbic DA and exerts complex modulatory actions on DA function. Two CCK receptor subtypes have been identified and selective antagoni sts have been developed. To examine the possible contribution of endog enous CCK mechanisms to individual differences in responsivity to AMP treatment, male Wistar rats were divided into low- and high-AMP respon ders based on a median split of their locomotor response to AMP and th e effects of the selective CCK antagonists L365-260 (CCKB; 0.01, 0.1, 0.5 mg/kg; n = 16) and devazepide (CCKA; 0.001, 0.01, 0.1 mg/kg; n = 2 3) were determined. Results showed that L365-260 (0.1 mg/kg) potentiat ed AMP-induced hyperactivity in low-AMP responders but did not affect AMP-induced hyperactivity in high-AMP responders. Devazepide was witho ut effect in both groups of animals. This pattern of results suggests that CCKB, but not CCKA, receptor mechanisms contribute to interindivi dual variation in responsivity to AMP.