Decreased M1 muscarinic receptor density in rat amphetamine model of schizophrenia is normalized by clozapine, but not haloperidol.
There is increasing evidence supporting the involvement of the muscarinic-cholinergic system in schizophrenia. We examined the M1 muscarinic receptor density and mRNA expression in brains of a rat amphetamine model of schizophrenia. We also assessed the effect of the model and chronic treatment with haloperidol and clozapine on brain M1 receptor density and gene expression. A significant decrease of about 20% in the density of M1 receptor was detected in the cortex and in the striatum of amphetamine model rats. A significant increase of 33% in the density of the M1 receptor was found in the cortex and striatum of rats treated chronically with clozapine (0.5 mg/kg), but not with haloperidol (25 mg/kg). Chronic clozapine, but not haloperidol, normalized the decrease in M1 receptors observed in amphetamine model rats, in both cortex and striatum. Regulation of the M1 receptor may occur in a post-transcriptional phase. Our findings suggest involvement of both dopaminergic and cholinergic-muscarinic systems in the pathophysiology and pharmacotherapy of schizophrenia.
Malkoff
Adi
A
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. adimalkoff@gmail.com
Weizman
Abraham
A
Gozes
Illana
I
Rehavi
Moshe
M
D000661:Amphetamine; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants; D003024:Clozapine / Q000627:therapeutic use*; D017931:DNA Primers; D006220:Haloperidol / Q000627:therapeutic use*; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D017931:DNA Primers; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D010890:Pirenzepine; D000661:Amphetamine; D003024:Clozapine; D006220:Haloperidol