The CCK‐B Antagonist CI‐988 Increases Dopamine Levels in Microdialysate from the Rat Nucleus Accumbens via a Tetrodotoxin‐ and Calcium‐Independent Mechanism

Abstract: CI‐988, a water‐soluble, selective cholecystokinin‐B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI‐988 produced three‐ to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI‐988 perfusion and returned to baseline levels upon cessation of CI‐988 perfusion. However, the cholecystokinin‐A antagonist CAM‐1481, and the relatively inactive enantiomer of CI‐988, CAM‐1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI‐988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI‐988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular.