Effects of cholecystokinin autagonists on the discriminative stimulus effects of cocaine in rats and monkeys

FRANÇAIS :
La cholécystolinine (CCK) est un modulateur de la neuratransmission de la dopamine dans les voies mésolimbiques, voies impliquées dans les effets de la cocaïne. L'action des antagonistes MK-329 (récepteurs A) et CI-988 (récepteurs B) de la CCK est étudiée sur des rats et des singes conditionnés à discriminer la cocaïne. Le MK-329 diminue la fonction dose-réponse de la cocaïne chez le rat, alors que le CI-988 n'altère pas systématiquement les effets de la cocaïne chez le rat ni chez le singe. Il semblerait donc peu probable que les antagonistes de récepteurs A de la CCK diminuent les effets subjectifs de la cocaïne.
ENGLISH :
Cholecystokinin (CCK) has been implicated as a modulator of dopamine (DA) neurotransmission in the mesolimbie DA pathway, a primary pathway implicated in the effects of cocaine related to its abuse. The present experiment was designed to examine whether an antagonist that acts at either CCK a or CCK b receptors can modify the discriminative stimulus effects of cocaine in animals. Rats and rhesus monkeys were trained in two-lever drug dscrimination paradigms to discriminate cocaine from saline. The CCK a antagonist MK-329 or the CCK b antagonist CI-988 were administered 30 min. before determination of cocaine dose-response functions using a cumulative dosing method. In monkeys, CI-988 was administered 30, 60, or 120 min. before the training dose of cocaine. In both species, cocaine produced dose-related increases in the percentage of responses emitted on the cocaine-appropriate lever. In rats, MK-329 shifted the cocaine dose-response function to the right in a dose-related manner. In contrast, CI-988 did not systematically alter the effects of cocaine in either rats or monkeys. Since drug discrimination serves as an animal model of the subjective effects of drugs in humans, these results suggest that CCK A antagonists may decrease the subjective effects of cocaine. It seems unlikely that CCK B antagonists will alter the subjective effects of cocaine.