The presence of high concentrations of both dopamine and cholecystokinin (CCK) in the striatum and in various limbic structures suggests that the CCK may not only influence dopaminergic transmission, but it also may be relevant to the psychopathology of schizophrenia and to the therapeutic effects of neuroleptics. By using a synaptosomal fraction isolated from the mouse cerebral cortex and propionyl-3HCCK8-sulphate (3HCCK8S) as a ligand, a single binding site for 3HCCK8 with aKdvalue of 1.04 nM and aBmaxvalue of 42.9 fmol/mg protein was identified. The competitive inhibition of 3HCCK8S binding by related peptides produced an order of potency of CCK8-sulphated (IC50=5.4 nM)>CCK8-unsulfated (IC50=40 nM) and>CCK4 (IC50=125 nM). The regional distribution of 3HCCK8S binding in the mouse brain was highest in the olfactory bulb (34.3±5.6 fmol/mg protein)>cerebral cortex>cerebellum>olfactory tubercle>striatum>pons-medulla>mid brain>hippocampus>hypothalamus (12.4±2.1 fmol/mg protein). The repeated administration of haloperidol (2.5 mg/kg/tid) increased the binding of 3HCCK8S in cerebral cortex from 31.8±1.7 to 38.9±5.2 fmol/mg protein. The varied distribution of CCK8S receptors may signify nonuniform functions for the octapeptide in the br
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