THE CCK-B ANTAGONIST CI-988 INCREASES DOPAMINE LEVELS IN MICRODIALYSATE FROM THE RAT NUCLEUS-ACCUMBENS VIA A TETRODOTOXIN-INDEPENDENT AND CALCIUM-INDEPENDENT MECHANISM

Cl-988, a water-soluble, selective cholecystokinin-B antagonist, was p erfused through a microdialysis probe into the anterior nucleus accumb ens, posterior nucleus accumbens, or caudate nucleus of anesthetized r ats. High concentrations of Cl-988 produced three- to fivefold increas es in dopamine overflow, at all three sites, that were temporally corr elated with the Cl-988 perfusion and returned to baseline levels upon cessation of Cl-988 perfusion. However, the cholecystokinin-A antagoni st CAM-1481, and the relatively inactive enantiomer of Cl-988, CAM-124 1, also increased dopamine overflow in the nucleus accumbens. Furtherm ore, the ability of Cl-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetro dotoxin treatment. The mechanism by which locally administered Cl-988 increases dopamine overflow appears not to be anatomically specific, n ot selective for one cholecystokinin receptor subtype, and may be nonv esicular.