Dopamine receptor elevation by cholecystokinin

High concentrations of cholecystokinin (CCK) in the striatum and limbic areas of the brain suggest that this peptide may influence dopaminergic transmission. Thus, the effect of CCK on dopamine D2 receptors in the striatum and nucleus accumbens of the rat brain both in vitro and in vivo (central and peripheral administration) was studied by determining the binding of 3H-spiperone. The density (Bmax) of D2 receptors was elevated (a) by 20% in the accumbens upon in vitro co-incubation with 10(-6) M CCK. (A non-significant drop of 10% occurred in the striatum); (b) by about 40% in the accumbens and 25% in the striatum after continuous intraventricular infusion of CCK for 24 hr. The increase in receptor density in the accumbens was maintained for 14 days and in both tissues was specific to CCK (neurotensin infusion did not alter 3H-spiperone binding); (c) by 20% in the accumbens and 15% in the striatum 3 hr after a single IP injection of 50 micrograms/kg CCK or caerulein, and maintained up to 14 days later. These results suggest that CCK elevates dopamine D2 receptors in the accumbens and striatum and may be a physiological modulator of the dopaminergic system.