Cholecystokinin octapeptide potentiates the inhibitory response mediated by D2 dopamine receptors in slices of the ventral tegmental area of the brain in the rat.
The ability of cholecystokinin octapeptide (CCK8) to modulate dopamine (DA)-induced inhibition of the firing of neurons in the ventral tegmental area of the rat was examined. Extracellular recordings were obtained from putative DA-containing neurons, identified on the basis of their electrophysiological characteristics and response to DA, in an in vitro slice preparation from the ventral tegmental area of the brain. Application of DA produced a concentration-dependent reduction in firing rate. This DA-induced inhibition was mimicked by the D2 selective agonist, LY 171555 (trans-(-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H- pyrazolo[3,4-g]quinoline), but not by the D1 selective agonist, SKF 38393 (R-(+)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine). The DA-induced inhibition was antagonized selectively by the D2 antagonist, l-sulpiride, but not by the D1 antagonist, SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol). However, CCK8 elicited a transient increase in firing rate in some neurons and, in addition, potentiated the inhibitory response evoked by DA or LY 171555. Again SKF 38393 was without effect following the administration of CCK8. Taken together, these results suggest that DA-induced inhibition of DA-containing neurons in the ventral tegmental area of the brain of the rat is mediated by activation of D2-receptors and that CCK8 potentiates this D2-mediated inhibition.
Neuroscience Research Division, Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois 60064.
J D
JD
Stittsworth
A L
AL
Mueller
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004594:Electrophysiology; D004873:Ergolines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*; D013469:Sulpiride / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism*
D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D012844:Sincalide