Cholecystokinin combined with serotonin in the hypothalamus limits accumbens dopamine release while increasing acetylcholine: a possible satiation mechanism

Serotonin (5-HT) or cholecystokinin (CCK) injected in the hypothalamic paraventricular nucleus (PVN) inhibits feeding, but the mechanism is unknown. Prior research suggests that dopamine (DA) input to the nucleus accumbens (NAc) motivates behavior, and a component of that motivation circuit includes hypothalamic feeding systems. Acetylcholine (ACh) in the NAc, on the other hand, may act in part to inhibit feeding and generate satiety. If so, 5-HT and/or CCK in the PVN should lower extracellular DA or release ACh in the NAc. Rats were prepared with microdialysis probes in the NAc and injectors in the PVN. Serotonin (7.75 μg) or CCK-8 (0.12 μg) injected in the PVN significantly decreased ipsilateral accumbens DA (63 and 73% of baseline, respectively, without effect on ACh). However, 5-HT plus CCK injected in combination decreased DA to 72% ( P