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Cholecystokinin Modulates the Release of Dopamine from the Anterior and Posterior Nucleus Accumbens by Two Different Mechanisms


Address correspondence and reprint requests to Dr. J. C. Hunter at Parke-Davis Research Unit, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QB, U.K.


Abstract: The effects of various cholecystokinin (CCK)-related peptides were investigated on 35 mM K+ -stimulated endogenous dopamine release from slices of either anterior or posterior nucleus accumbens of the rat. CCK sulphated octapeptide (1–10 μM), but not pentagastrin or CCK unsulphated octapeptide, was found to cause a dose-dependent increase in the release from the posterior nucleus accumbens. This effect was blocked by low doses of the CCKA receptor antagonist L364,718 (10 nM) but not the CCKB receptor antagonist L365,260. In the anterior nucleus accumbens CCK sulphated octapeptide (1 μM) and CCK unsulphated octapeptide (0.1–1 μM) inhibited the dopamine release, and this effect was blocked by L365,260 (10–100 nM) but not by L364,718. These results suggest that CCK has a different effect on dopamine release from the anterior and posterior nucleus accumbens and that these effects are mediated by two different types of CCK receptor.