Individual differences in the response of dopamine receptor number to chronic haloperidol treatment

Previous studies of the haloperidol-induced increase in dopamine (DA) receptor numbers have not emphasized the existence of individual differences. The present study evaluated DA receptor number in individual rat and mouse caudates after haloperidol or drug-free feeding. After 3 months of haloperidol treatment of rats there was a 78% increase in caudate DA receptor number, accompanied by a significantly increased variance in the number of DA receptors in haloperidol-treated compared with control rats. Although three inbred mouse strains (Balb/C, C3H, and CBA) also showed significant increases in DA receptor number after 3 months of haloperidol treatment, no increased variance was observed after haloperidol treatment. Wild-type mice from a genetically heterogenous population showed increases in DA receptor number after chronic haloperidol treatment accompanied by a significantly increased variance in receptor number of the drug-treated group. These findings suggest that pharmacogenetic factors may be important in determining the magnitude of DA receptor response to long-term neuroleptic treatment.