The effects of cholecystokinin on the in vivo release of newly synthesized [3H]dopamine from the nucleus accumbens of the rat.
It has been reported that in the medial nucleus accumbens (NAc) there are nerve terminals which contain either the neuropeptide cholecystokinin (CCK) or the catecholamine dopamine (DA), as well as terminals which contain both. In this study, we have examined the action of CCK-peptides on the basal and potassium-evoked release of [3H]DA within this structure. The in vivo release of [3H]DA, newly synthesized from [3H]tyrosine, was measured by using the push-pull cannula perfusion technique. It appeared that a large percentage of the [3H]DA released under resting conditions was dependent upon nerve impulse activity as it was found that tetrodotoxin, absence of extracellular Ca2+, and the inhibition of DA synthesis by alpha-methyl-p-tyrosine all decreased [3H]DA release by more than 50%. In addition, the potassium-evoked release of [3H]DA was found to be almost completely dependent upon extracellular Ca2+. When sulfated CCK-octapeptide was administered into the NAc, it was found to increase the basal levels of [3H]DA released at concentrations of 2 X 10(-8) and 2 X 10(-7) M. However, at 2 X 10(-6) M there was no longer an effect by this peptide. The unsulfated form was found to have no effect at a concentration which was maximally effective for the sulfated form. In contrast to its effects on the basal release of [3H]DA, sulfated CCK-octapeptide was found to attenuate the potassium-evoked release of [3H]DA from the NAc in a concentration-dependent fashion from 2 X 10(-9) to 2 X 10(-6) M. The unsulfated form of the octapeptide had no effect on evoked release. Our results suggest that CCK acts to modulate the release of DA within the NAc in vivo in a complex manner, as it appears that the action of CCK depends not only on the concentration tested but also on the excitation state of the tissue during the testing period.
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D014316:Tritium; D013779:Tetrodotoxin; D019805:alpha-Methyltyrosine; D002766:Cholecystokinin; D012844:Sincalide; D011188:Potassium; D004298:Dopamine