CHOLECYSTOKININ-OCTAPEPTIDE IN-VITRO AND EX-VIVO STRONGLY MODULATES STRIATAL DOPAMINE D-2 RECEPTORS IN RAT FOREBRAIN SECTIONS

Receptor autoradiographic experiments together with the filter wipe-of f technique were performed to investigate the effects of cholecystokin in octapeptide (CCK-8) on dopamine De receptors. In vitro studies show ed that 1 nM CCK-8 significantly increased the K-D value of binding si tes for the D-2 agonist [H-3]N-propylnorapomorphine (NPA) in the rostr al and caudal parts of the nucleus accumbens by 48 and 148% respective ly. In contrast, 1 nM CCK-8 significantly decreased the IC50 value of dopamine for binding sites for the D-2 antagonist [I-125]iodosulpride in the rostral and caudal parts of the caudate-putamen by 46 and 56% r espectively, and in the rostral and caudal parts of the nucleus accumb ens (areas of CCK-dopamine coexistence) by 57 and 75% respectively, Ex vivo studies demonstrated that 30 min after an intraventricular injec tion of 1 nmol/rat CCK-8 the K-D value of [H-3]NPA binding sites in th e caudal part of the forebrain and the IC50 value of dopamine for [I-1 25]iodosulpride binding sites in the caudal part of the nucleus accumb ens were significantly increased by 160% and decreased by 77% respecti vely. These results indicate for the first time that in sections CCK-8 in vitro and ex vivo can strongly regulate D-2 receptor affinity in t he striatum. The present studies also provide evidence for stronger mo dulation of D-2 receptors by CCK-8 in the area of CCK/dopamine coexist ence in the nucleus accumbens than in other basal ganglion areas, supp orting the existence of CCK/D-2 receptor interactions in cotransmissio n. The stronger interactions found in sections than in membrane prepar ations may indicate the requirement of intracellular mechanisms and/or a more intact membrane structure for optimal receptor-receptor intera ctions.