title: Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann's areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment.
abstract: OBJECTIVE
  Aberrant cholinergic inputs and synaptic neurotransmission in the prefrontal cortex induce cognitive impairment, which is a central feature of schizophrenia. Postsynaptic excitatory muscarinic cholinergic M(1) and M(4) receptors are the major cholinoceptive targets in the prefrontal cortex and hence may be involved in the pathology and/or pharmacotherapeutics of schizophrenia.
  
  
  METHODS
  Using quantitative autoradiography, the authors analyzed the binding of the M(1)/M(4) receptor selective antagonist [(3)H]pirenzepine in prefrontal cortex (Brodmann's areas 8, 9, 10, and 46) from schizophrenia patients who had (N=6) or had not (N=11) been treated with the anticholinergic agent benztropine mesylate and from normal comparison subjects (N=20). Moreover, preliminary studies of [(3)H]pirenzepine binding in rat frontal cortex following administration of antipsychotic drugs or benztropine mesylate were performed.
  
  
  RESULTS
  Relative to those of comparison subjects, the mean levels of [(3)H]pirenzepine binding were significantly lower in Brodmann's areas 9 and 46 of the schizophrenia patients not treated with benztropine mesylate (18% lower in Brodmann's area 9 and 21% lower in Brodmann's area 46) and in all four examined regions of the patients who had received benztropine (51%-64% lower). Antipsychotic or anticholinergic drugs tended to increase or have no effect on the density of [(3)H]pirenzepine-labeled receptors in rat frontal cortex.
  
  
  CONCLUSIONS
  Because M(1) and M(4) receptors are critical to the functions of prefrontal cortical acetylcholine, the present findings suggest a functional impairment in cholinergic neurotransmission in schizophrenia and the possibility that muscarinic receptors are involved in the pharmacotherapeutics of the disorder.
authors.affiliation: Department of Otolaryngology, Royal Victorian Eye and Ear Hospital, 32 Gisborne St., East Melbourne, Victoria 3002, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Crook
authors.forename: E
authors.initials: E
authors.lastname: Tomaskovic-Crook
authors.forename: D L
authors.initials: DL
authors.lastname: Copolov
authors.forename: B
authors.initials: B
authors.lastname: Dean
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001345:Autoradiography; D001590:Benztropine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010276:Parasympatholytics / Q000494:pharmacology / Q000627:therapeutic use; D010890:Pirenzepine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D014316:Tritium; D001590:Benztropine; D010890:Pirenzepine