Cholecystokinin modulates both the development and the expression of behavioral sensitization to amphetamine in the rat.
BACKGROUND
Repeated administration of psychostimulants such as amphetamine (AMPH) produces an enduring augmentation of their locomotor effects. Previous research suggests that this phenomenon, termed sensitization, is related to changes within the mesolimbic dopamine (DA) system.


OBJECTIVE
The present experiments were designed to investigate the contribution of endogenous cholecystokinin (CCK), a neuropeptide co-localized with DA in the mesolimbic system, to the development (experiment 1) and the expression (experiment 2) of locomotor sensitization to AMPH.


METHODS
In experiment 1, rats were injected (IP) with the CCK(A) antagonist devazepide (0, 0.001, 0.01, or 0.1 mg/kg) or the CCK(B) antagonist L-365,260 (0, 0.001, 0.01, 0.1, or 1.0 mg/kg) followed by AMPH (1.5 mg/kg) once daily for seven days. Following 10 days withdrawal, rats were administered AMPH (0.75 mg/kg) and their locomotor activity recorded. In experiment 2, rats were administered AMPH (1.5 mg/kg) once daily for 7 days. Following 10 days withdrawal, rats were injected with devazepide (0, 0.0001, 0.001, 0.01, 0.1, or 1.0 mg/kg) or L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg) followed 30 min later by AMPH (0.75 mg/kg) and their locomotor activity recorded.


RESULTS
When administered during the AMPH pretreatment phase of experiment 1, the two highest doses of L-365,260 attenuated, and the lowest dose of L-365,260 potentiated, the sensitized locomotor response to AMPH challenge. When administered prior to the AMPH challenge phase of experiment 2, devazepide attenuated the sensitized locomotor response to AMPH.


CONCLUSIONS
These results suggest that CCK(B) and CCK(A) receptors modulate the development and the expression of behavioral sensitization to AMPH, respectively.
Wunderlich
G R
GR
Department of Psychology, University of Toronto, Ontario, Canada.
DeSousa
N J
NJ
Vaccarino
F J
FJ
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010671:Phenylurea Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
D001570:Benzodiazepinones; D000697:Central Nervous System Stimulants; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D000661:Amphetamine; D020109:Devazepide