Treatment with haloperidol or clozapine causes changes in dopamine receptors but not adenylate cyclase or protein kinase C in the rat forebrain

Abstract

The effect of treating rats with daily injections of haloperidol (1 mg/kg/day) or clozapine (20 mg/kg/day) for four weeks on second messengers and dopamine receptors was studied. The binding of [3H]forskolin to adenylate cyclase (AC), [3H]phorbol 12,13-dibutyrate (PDBu) to protein kinase C (PKC), [3H]SCH23390 binding to the dopamine D1 (DA-D1) receptor and [3H]spiperone binding to the dopamine D2 (DA-D2) receptor were measured using quantitative autoradiography. The density of AC was greatest in the caudate-putamen, nucleus accumbens and olfactory tubercle, a distribution resembling that of DA-D1 receptor. The distribution of PKC was relatively homogeneous in the forebrain. Neither haloperidol nor clozapine administration significantly altered the levels of AC or PKC in the caudate-putamen. By contrast treatment with haloperidol, but not clozapine, significantly increased the density of DA-D2 receptors in the caudate-putamen without affecting the density of DA-D1 receptors. By contrast, both haloperidol and clozapine increased the density of DA-D1 receptors in the olfactory tubercle.