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

• Published in: Life sciences (1973) Vol. 59; no. 23; pp. 2001 - 2008
• Main Authors: Wan, David C., Dean, Brian, Pavey, Geoffrey, Copolov, David L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.11.1996
• Subjects: adenylate cyclase; Adenylyl Cyclases - drug effects; Adenylyl Cyclases - metabolism; Animals; clozapine; Clozapine - pharmacology; Clozapine - therapeutic use; dopamine receptors; forebrain; haloperidol; Haloperidol - pharmacology; Haloperidol - therapeutic use; Male; Prosencephalon - drug effects; Prosencephalon - enzymology; Prosencephalon - metabolism; protein kinase C; Protein Kinase C - drug effects; Protein Kinase C - metabolism; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Dopamine - drug effects; Receptors, Dopamine - metabolism; Second Messenger Systems; haloperidol; clozapine; forebrain; dopamine receptors; adenylate cyclase; protein kinase C
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(96)00551-6

The effect of treating rats with daily injections of haloperidol (1mg/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 D 1 (DA-D 1) receptor and [ 3H]spiperone binding to the dopamine D 2 (DA-D 2) 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-D 1 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-D 2 receptors in the caudate-putamen without affecting the density of DA-D 1 receptors. By contrast, both haloperidol and clozapine increased the density of DA-D 1 receptors in the olfactory tubercle.