Evidence for the contribution of CCKB receptor mechanisms to individual differences in amphetamine-induced locomotion.
Recent evidence shows that rats exhibit individual differences in their locomotor 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 selective antagonists 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 (CCKA; 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 CCKB, but not CCKA, receptor mechanisms contribute to interindividual variation in responsivity to AMP.
Addiction Research Foundation, University of Toronto, Ontario, Canada.
G A
GA
Higgins
T L
TL
Sills
D M
DM
Tomkins
E M
EM
Sellers
F J
FJ
Vaccarino
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology; D020109:Devazepide; D007206:Individuality; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D000661:Amphetamine; D020109:Devazepide