Treatment with haloperidol or clozapine causes changes in dopamine receptors but not adenylate cyclase or protein kinase C in the rat forebrain.
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.
Wan
D C
DC
NH&MRC Schizophrenia Research Unit, Mental Health Research Institute of Victoria, Parkville, Australia.
Dean
B
B
Pavey
G
G
Copolov
D L
DL
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016548:Prosencephalon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D015290:Second Messenger Systems
D011954:Receptors, Dopamine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D003024:Clozapine; D006220:Haloperidol