Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine.
Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in the CNS may be important in the pathogenesis of psychotic disorders and substance abuse. In this study, the effect of coadministration of the selective CCK receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and CCK2 receptors, respectively), on the effect of amphetamine on the rat exploratory behavior, and on sensitization of locomotor response to amphetamine, were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the exploration box for 5 consecutive testing days, while devazepide (10 microg/kg) blocked and L-365,260 (10 microg/kg) enhanced amphetamine-induced stimulation of activity. Devazepide coadministration prevented the development of sensitization to amphetamine, while coadministration of L-365,260 with amphetamine potentiated the locomotor effect of a challenge dose of amphetamine. These results suggest that endogenous CCK, released during exploratory activity, shapes behavioral responses to amphetamine by acting on both receptor subtypes, and modulates the development of sensitization to amphetamine.
Alttoa
Aet
A
Department of Psychology, Center of Behavioral and Health Sciences, Tartu University, Tiigi 78, 50410 Tartu, Estonia.
Harro
Jaanus
J
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D000697:Central Nervous System Stimulants; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D000661:Amphetamine; D020109:Devazepide