Evidence for CCK(A) receptor involvement in the acquisition of conditioned activity produced by cocaine in rats.
Cholecystokinin (CCK) is co-localized with dopamine (DA) in the nucleus accumbens (NAC) where evidence suggests that CCK(B) receptor-mediated mechanisms inhibit, while CCK(A) receptor-mediated mechanisms facilitate, DA function. As DA has been implicated in the acquisition of conditioned activity, the present experiments investigated the effects of CCK(A) and CCK(B) receptor selective antagonists on the acquisition and expression of conditioned activity produced by cocaine. Paired rats received four cocaine-environment pairings whereas Unpaired rats received the two stimuli explicitly unpaired, in that they received cocaine in the home cage. Using this procedure, cocaine (10 mg/kg, i.p.) reliably produced conditioned activity such that the Paired group showed a higher level of locomotion than the Unpaired group on a subsequent drug-free test day. Systemic administration of devazepide, a CCK(A) receptor antagonist, but not L-365,260, a CCK(B) receptor antagonist, blocked the acquisition of conditioned activity. Microinjection of the CCK(A) antagonist PD-140548 into the NAC similarly impaired the acquisition of conditioned activity. However, systemic administration of neither the CCK(A) nor CCK(B) receptor antagonist modified the expression of cocaine-induced conditioned activity once established. These studies suggest that CCK(A), but not CCK(B), receptor mediated mechanisms in the NAC play a key role in the acquisition of conditioned activity.
Josselyn
S A
SA
Department of Psychology, University of Toronto, Ont., Canada.
De Cristofaro
A
A
Vaccarino
F J
FJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology
D001570:Benzodiazepinones; D007211:Indoles; C102662:PD 140548; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C058121:L 365260; D003042:Cocaine