Chronic thioridazine treatment differently affects DA receptors in striatum and in mesolimbo-cortical systems

Chronic thioridazine administration (5 mg/kg for 22 days) caused both behavioral and dopamine (DA) receptor modifications in rats. After chronic thioridazine administration, a significant increase in both locomotion and stereotypies induced by apomorphine was observed. In particular, only sniffing increased significantly, whereas grooming behavior decreased and the number of rearings did not change. Autoradiographic data were consistent with the behavioral results. Chronic thioridazine caused an up-regulation of DA receptors both in the striatum and in the olfactory tubercle (O.T.). The striatal effect may account for the increase of stereotypies, whereas the effect in the olfactory tubercle may account for the increase in locomotion. An increase in DA receptors was also found in the medial (MCTX) and dorsal cortex (DCTX). However, a decrease in DA receptors appeared in the nucleus accumbens septi (NAS) and in the lateral cortex (LCTX). This decrease, selectively localized in the mesolimbic DA system, may represent the neurobiological substrate of the depolarization block observed in A10 neurons after chronic thioridazine treatment.