Increase in brain 125I-cholecystokinin (CCK) receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions.
Specific 125I-CCK receptor binding was significantly increased in brain tissue taken from guinea pig or mouse following chronic (2-3 week) daily administration of haloperidol (2-3 mg/kg/day). Scatchard analysis indicated the increase in CCK binding was due to an increased receptor number (B max) with no change in affinity (Kd). In guinea pigs, the increased CCK binding was observed in the mesolimbic regions and frontal cortex, but not in striatum, hippocampus nor posterior cortex. In mice, however, the increases occurred in both pooled cerebral cortical-hippocampal tissue, and in the remainder of the brain. Enhanced CCK receptor binding was also observed in membranes prepared from whole brain of mice one month following intracisternal injection of 6-hydroxydopamine. Additionally, an increase in CCK binding was observed in mesolimbic regions and frontal cortex, but not striatum or hippocampus, of guinea pigs 3 weeks after an unilateral radiofrequency lesions of the ipsilateral ventral tegmentum. The present studies demonstrate that three different procedures which reduce dopaminergic function in the brain enhance CCK receptor binding. The data provide further support for a functional interrelationship between dopaminergic systems and CCK in some brain regions and raise the possibility that CCK may play a role in the antipsychotic action of neuroleptics.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002766:Cholecystokinin / Q000378:metabolism*; D004343:Drug Implants; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D016627:Oxidopamine; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D013681:Tegmentum Mesencephali / Q000378:metabolism
D004343:Drug Implants; D006892:Hydroxydopamines; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D016627:Oxidopamine; D002766:Cholecystokinin; D006220:Haloperidol