Cholecystokinin Octapeptide In Vitro and Ex Vivo Strongly Modulates Striatal Dopamine D2 Receptors in Rat Forebrain Sections

Receptor autoradiographic experiments together with the filter wipe-off technique were performed to investigate the effects of cholecystokinin octapeptide (CCK-8) on dopamine D₂ receptors. In vitro studies showed that 1 nM CCK-8 significantly increased the K_D value of binding sites for the D₂ agonist [³H]N-propylnorapomorphine (NPA) in the rostral and caudal parts of the nucleus accumbens by 48 and 148% respectively. In contrast, 1 nM CCK-8 significantly decreased the IC₅₀ value of dopamine for binding sites for the D₂ antagonist [¹²⁵I]iodosulpride in the rostral and caudal parts of the caudate-putamen by 46 and 56% respectively, and in the rostral and caudal parts of the nucleus accumbens (areas of CCK-dopamine coexistence) by 57 and 75% respectively. Ex vivo studies demonstrated that 30 min after an intraventricular injection of 1 nmol/rat CCK-8 the K_D value of [³H]NPA binding sites in the caudal part of the forebrain and the IC50 value of dopamine for [¹²⁵I]iodosulpride binding sites in the caudal part of the nucleus accumbens were significantly increased by 160% and decreased by 77% respectively. These results indicate for the first time that in sections CCK-8 in vitro and ex vivo can strongly regulate D₂ receptor affinity in the striatum. The present studies also provide evidence for stronger modulation of D₂ receptors by CCK-8 in the area of CCW-dopamine coexistence in the nucleus accumbens than in other basal ganglion areas, supporting the existence of CCWD₂ receptor interactions in cotransmission. The stronger interactions found in sections than in membrane preparations may indicate the requirement of intracellular mechanisms and/or a more intact membrane structure for optimal receptor-receptor interactions.