Pharmacological and mechanistic studies of cholecystokinin-facilitated [3H]dopamine efflux from rat nucleus accumbens.
Cholecystokinin (CCK) is co-localized with dopamine (DA) in mesolimbic neurons of the CNS and appears to selectively regulate the output of this system. In an attempt to characterize the nature of CCK interactions with mesolimbic DA-containing nerve terminals, we have investigated CCK regulation of [3H]DA overflow from rat nucleus accumbens slices. CCK-8 produced a saturable and potent (EC50 = 3 nM) facilitation of KCl (35 mM)-evoked [3H]DA efflux from nucleus accumbens, but failed to significantly alter [3H]DA efflux from striatum: The stimulatory action of CCK-8 was unaffected by the muscarinic antagonist atropine, the opiate antagonist naloxone, or the selective ion channel blockers tetrodotoxin and nifedipine. Pharmacological studies revealed that non-sulfated CCK-8 and CCK-4 (up to low micromolar concentrations) did not facilitate [3H]DA efflux from accumbens slices. Furthermore, the effect of CCK-8 was selectively and potently (IC50 = 300 nM) inhibited by the Type A-selective CCK antagonist CR-1409. Taken together, these results indicate that CCK regulates DA efflux from mesolimbic nerve terminals via a direct presynaptic action on receptors which display a pharmacological profile that is similar to Type A CCK receptors in gastrointestinal tissues.
Vickroy
T W
TW
Abbott Laboratories, Pharmaceutical Discovery, Abbott Park, Illinois 60064.
Bianchi
B R
BR
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology
D007473:Ion Channels; D011954:Receptors, Dopamine; D002766:Cholecystokinin; D012844:Sincalide; D004298:Dopamine