Reversal by cholecystokinin of apomorphine-induced inhibition of dopamine release in the nucleus accumbens of the rat.
In vivo electrochemical techniques were used to study the effects of the sulfated (CCK8-S) and unsulfated (CCK8-US) forms of cholecystokinin octapeptide on apomorphine-induced inhibition of dopamine (DA) release in the nucleus accumbens of the anesthetized rat. A dose-dependent inhibition of DA release was observed with intravenous (i.v.) injections of apomorphine. CCK8-S administered i.v. at the nadir of the apomorphine-induced inhibition of DA release produced a transient and dose-dependent increase followed by a prolonged decrease in DA release CCK8-US was ineffective in altering apomorphine's inhibitory effects on DA release. The CCK receptor antagonist proglumide injected i.v. 10 min after apomorphine administration had no effect on apomorphine-induced inhibition of DA release, but blocked the effects of CCK8-S on this inhibition. Given that apomorphine may inhibit DA release by a direct hyperpolarizing action on DA neurons, the observation that CCK8-S temporarily reverses apomorphine-induced effects and further inhibits DA release suggests that CCK8-S exerts its inhibitory effects via a process of depolarization block in DA neurons. These findings indicate that apomorphine and CCK8-S may inhibit DA release in vivo by opposite effects on DA cell membrane potentials and suggest that endogenously released CCK may serve to modulate mesolimbic DA neurotransmission.
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D002462:Cell Membrane / Q000187:drug effects; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*
D002766:Cholecystokinin; D011377:Proglumide; D001058:Apomorphine; D004298:Dopamine