CCK-8 excites substantia nigra dopaminergic neurons by increasing a cationic conductance.

Using the whole-cell patch-clamp technique, we investigated electrophysiological effects of cholecystokinin on acutely isolated dopaminergic (DA) neurons of rat substantia nigra (SN). During voltage-clamp recordings, sulfated cholecystokinin octapeptide (CCK-8) dose-dependently induced an inward current at the holding potential of -7O mV. Under current-clamp recordings, CCK-8 depolarized DA neurons and triggered action potentials. CCK-8-evoked inward current reversed its direction at 1.0 +/- 1.9 mV (n = 9), and the amplitude of inward current induced by CCK-8 was reduced in an external solution with low sodium concentration. Cholecystokinin tetrapeptide (CCK-4), a selective CCK-B receptor agonist, failed to induce an inward current. CCK-8-evoked cationic current was antagonized by lorglumide, a selective CCK-A receptor antagonist. PD135, 158, a highly selective and potent CCK-B receptor antagonist, failed to attenuate CCK-8-induced cationic currents. These results suggest that by activating CCK-A receptors, CCK-8 excites SN DA neurons via increasing a non-selective cationic conductance.