Typical and atypical antipsychotic occupancy of D 2 and S 2 receptors: An autoradiographic analysis in rat brain

Abstract

In thin sections of rat brain, [ 3H]spiperone binds to D 2 sites in the basal ganglia (caudate-putamen, nucleus accumbens, olfactory tubercle) and S 2 sites in the claustrum and motor cortex. The in vitro displacement of [ 3H]spiperone from these regions was quantified autoradiographically with the “atypical” neuroleptics clozapine and thioridazine, which ameliorate psychosis, a “typical” neuroleptic, haloperidol, which also induces extrapyramidal side effects, or with metoclopramide, which induces extrapyramidal side effects but is an ineffective antipsychotic. Whereas metoclopramide was equipotent at D 2 sites, haloperidol was less potent and clozapine and thioridazine more potent by 2- to 3-fold at competing for D 2 sites in the nucleus accumbens or olfactory tubercle than in the caudate-putamen. As measured autoradiographically or with tissue homogenates, clozapine, thioridazine, and five other atypical neuroleptics were 4- to 800-times more potent at competing for S 2 sites in the frontal cortex than for D 2 sites in the basal ganglia. A preference of atypical antipsychotics for D 2 receptors in the nucleus accumbens and olfactory tubercle and for the S 2 receptor may explain the relative lack of extrapyramidal side effects produced by these compounds.