Effects of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT 2) and dopamine (D 2) receptors in the rat brain

Abstract

The effects of acute and chronic treatments with haloperidol or clozapine on the binding of [ 3H]spiperone to D 2 and 5-HT 2 receptors were examined in 6 discrete regions of the striatum, n. accumbens and frontal cortex using quantitative autoradiography. Acute treatment with haloperidol, 0.1–2.0 mg/kg, i.p., produced a dose-dependent reduction to 60% of control in the binding of [ 3H]spiperone to D 2 receptors in the striatum and n. accumbens and no effect on the binding of [ 3H]spiperone to 5-HT 2 receptors in the striatum, n. accumbens or frontal cortex. Acute treatment with clozapine, 10–40 mg/kg, i.p., produced a dose-dependent reduction in D 2-specific binding in both the n. accumbens and the striatum and also significant reductions to 24% of control in the binding of [ 3H]spiperone to cortical 5-HT 2 receptors. Chronic treatment with haloperidol, 1 mg/kg/day, i.p., significantly increased (40–65%) the maximal number of D 2-specific [ 3H]spiperone binding sites in the n. accumbens and the dorsolateral and ventrolateral regions of the striatum, whereas small increases (20–29%) were seen in the ventromedial, dorsomedial, rostral and caudal regions of the striatum. Chronic treatment with clozapine, 20 mg/kg/day, i.p., did not change the maximal number of D 2 receptors in the n. accumbens or any region of the striatum. Chronic treatments with clozapine produced a decrease in the maximal number of cortical 5-HT 2 receptors to 55% of control haloperidol had no effect. This study demonstrates regional differences in the up-regulation of striatal D 2 receptors following chronic treatment with haloperidol and different effects of a typical and atypical neuroleptic on 5-HT 2 receptors following acute and chronic treatments.