Effects of Typical and Atypical Antipsychotic Drugs on Rat Brain Muscarinic Receptors

Quantitative in vitro autoradiography was used to examine changes in muscarinic M1/M4 and M2/M4 receptors (targeted with ³H]pirenzepine and ³H]AF-DX384 respectively), in rats treated with the typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic medications for a period of 36 days. Rats were sacrificed at either 2 h or 48 h after the last drug administration to examine immediate effects as well as the effects at 48 h after drug withdrawal. Haloperidol significantly increased ³H]pirenzepine binding in the dentate gyrus (37%) and in the CA1 region of the hippocampus (34%) in animals sacrificed 2 h after the last drug administration compared to controls. Similarly, clozapine significantly increased ³H]pirenzepine binding in dentate gyrus (29%) in rats sacrificed 2 h after the last drug administration compared to controls. Haloperidol decreased ³H]AF-DX384 binding in the basolateral nucleus of the amygdala (20%) in the rats sacrificed 48 h after the last drug administration compared to controls. These findings suggest that muscarinic receptors and limbic brain regions such as hippocampus and amygdala might represent common targets that mediate beneficial clinical effects of antipsychotic drugs.