SUBCHRONIC ADMINISTRATION OF CLOZAPINE, BUT NOT HALOPERIDOL OR METOCLOPRAMIDE, DECREASES DOPAMINE D-2 RECEPTOR MESSENGER-RNA LEVELS IN THE NUCLEUS-ACCUMBENS AND CAUDATE-PUTAMEN IN RATS

The effects of unique profile antipsychotic drugs on dopamine D-2, rec eptors and D-2 receptor messenger RNA were assessed Following subchron ic administration in rats. Male, Sprague-Dawley rats were administered oral haloperidol, clozapine, metoclopramide or no drug for three week s via their drinking water. Tissue from the medial nucleus accumbens a nd dorsolateral caudate-putamen was dissected and analyzed by Northern blot analysis for levels of dopamine D-2 receptor messenger RNA and b inding assays conducted with [H-3]spiperone for dopamine D-2 receptors . Haloperidol and metoclopramide, but not clozapine, significantly inc reased [H-3]spiperone in the caudate-putamen, but not the nucleus accu mbens. Clozapine significantly decreased D-2 messenger RNA levels in t he caudate-putamen and the nucleus accumbens, while metoclopramide and haloperidol had no significant effect in either brain region. The fin ding of decreased D2 receptor messenger RNA levels produced by subchro nic clozapine may account for the lack of striatal D2 receptor up-regu lation, which was robustly observed after subchronic haloperidol and m etoclopramide. Furthermore, since haloperidol and metoclopramide have a high liability for motor side effects, the current results relate fa vorably to the low motor side effect profile of clozapine.