CCK-8 modulation of mesolimbic dopamine: Antagonism of amphetamine-stimulated behaviors

Rats (N=15) were implanted with cannulae above the dopaminergic A10 ventral tegmental area (VTA). Two weeks later, four measures of open field behavior were quantified for 10 minutes commencing 30 minutes after parenteral d-amphetamine (1.5 mg/kg) and directly after bilateral infusion of 1.5 μl of: (a) artificial CSF only (VEH), (b) 1.25 μg desulfated CCK (DS-CCK), or (c) 1.25 μg sulfated CCK (CCK). Additional rats with bilateral cannulae directed toward the A10 terminal zones of nucleus accumbens were similarly tested with either VEH (N=2) or sulfated CCK (N=2). With VTA infusions, both the number of occurrences and duration of rearing were significantly reduced in CCK rats, while neither the number of square crossings nor duration of forward locomotion were significantly modified from controls. With nuclei accumbens septi (NAS) infusions, CCK-8 reduced rearing behavior more than ambulatory behavior in this preliminary testing. With either VTA or NAS infusions, no significant differences from controls were found upon two derived measures of motoric performance, namely, “velocity” (number of squares crossed per second in locomotion) and “vertical stability” (seconds per rear). These results suggest a modulation of dopaminergically-mediated behavior by (sulfated) CCK-8 at the cell body region and terminal fields of the mesolimbic (A10) dopamine system.