Receptor selectivity of cholecystokinin effects on mesoaccumbens dopamine neurons.
Extracellular recording techniques were combined with antidromic stimulation to examine the effects of C-terminal cholecystokinin (CCK) fragments and CCK antagonists on the activity of identified mesoaccumbens dopamine (MADA) neurons in chloral hydrate-anesthetized rats. These experiments were designed to determine the receptor selectivity of sulfated CCK octapeptide (CCK-8S) effects on MADA cells. Neither CCK tetrapeptide (CCK-4) nor unsulfated CCK octapeptide (CCK-8U) significantly altered MADA cell basal firing rate or responsiveness to the inhibitory effects of the D2 DA agonist quinpirole. As reported previously for ventral tegmental area DA cells, CCK-8S produced increases or decreases in the firing rate of most MADA cells sampled. CCK-8S also enhanced the sensitivity of MADA neurons to quinpirole-induced inhibition. This increase in sensitivity to quinpirole was blocked by pretreatment with the nonselective CCK receptor antagonist proglumide and the preferential CCK-A receptor antagonist CR 1409 but not by the preferential CCK-B receptor antagonist L-365,260. The inactivity of CCK-4 and CCK-8U in these tests and the results with the antagonists suggest that the effects of CCK-8S on MADA neuronal activity are mediated by CCK-A receptors.
Kelland
M D
MD
Laboratory of Neurophysiology, Center for Cell Biology, Sinai Research Institute, Detroit, MI 48235.
Zhang
J
J
Chiodo
L A
LA
Freeman
A S
AS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D004298:Dopamine / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010671:Phenylurea Compounds; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects*
D001570:Benzodiazepinones; D004873:Ergolines; D010455:Peptides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D019257:Quinpirole; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide; D004298:Dopamine