Dual modulation of dopamine release from anterior nucleus accumbens through cholecystokinin-B receptor subsites

Previous binding studies have suggested the existence of two affinity states for cholecystokinin-B (CCK-B) receptor. One study, using BC 197 and BC 264, two highly selective CCK-B agonists, has shown that BC 197 is selective for one subsite, B1, and that BC 264 has the same affinity for the two subsites, B1 and B2. Therefore, the possible involvement of CCK-B subsites in the modulation of endogenous dopamine (DA) release from slices of the anterior part of the nucleus accumbens was investigated with these two agonists in order to associate a functional response with activation of each subsite. The selective B1 agonist BC 197 produced a dose-dependent increase of 35 mM K(+)-stimulated DA release. In contrast, at a low concentration (20 nM), BC 264 inhibited the K(+)-evoked DA release, whereas at a higher concentration (1 microM), it stimulated the DA release. These two opposing effects were suppressed by the CCK-B antagonist PD-134,308, but not by the CCK-A antagonist L-364,718 and were not prevented by tetrodotoxin, a Na(+)-channel blocker. Moreover, BC 264 at 20 nM, in the presence of PD-134,308 at a concentration that would block the B2 subsites (0.1 nM), increased the evoked DA release. All together, these results support further the existence of distinct CCK-B subsites and suggest that, in the anterior nucleus accumbens, their stimulation mediates opposite effects on K(+)-stimulated DA release via a presynaptic mechanism.