Modulation of cholecystokinin release from posterior nucleus accumbens by D-2 dopamine receptor

The effect of specific D-2 dopamine (DA) receptor agonists and antagonists on potassium (55 mM)-evoked release of cholecystokinin-like immunoreactivity (CCK-LI) was studied in tissue slices of the rat posterior nucleus accumbens (NAc). Incubating the tissue slices in 100 nM or 1 microM of LY-141865, a specific D-2 DA receptor agonist, reduced the release of CCK-LI as indicated by a significant decrease in the S2/S1 ratio. Addition of 10 microM of (-)-sulpiride, a specific D-2 DA receptor antagonist, blocked the inhibitory effect of 100 nM of LY-141865 on the release of CCK-LI. In contrast, 10 microM of the specific D-1 DA receptor antagonist SCH 23390 was unable to attenuate the decrease in release of CCK-LI caused by 100 nM of LY-141865. Furthermore, the active isomer of LY-141865, LY-171555 at 0.1 to 50 nM, also decreased the release of CCK-LI from the tissue slices, while the inactive isomer, LY-181990 at 1 nM, did not affect CCK-LI release. The inhibitory effect of LY-171555 on the release of CCK-LI was lost when its concentration was increased to 100 nM, thus revealing a biphasic effect of D-2 DA receptor stimulation on the release of CCK-LI. These results demonstrate that stimulation of D-2 DA receptor can modulate the release of CCK from in vitro slices of the rat posterior NAc.