title: Effects of benzodiazepine treatment on cortical GABA(A) and muscarinic receptors: studies in schizophrenia and rats.
abstract: Changes in cortical γ-aminobutyric acid A (GABA(A)) receptors and muscarinic receptors have been reported in schizophrenia, a disorder treated with antipsychotic drugs and benzodiazepines. As there is a reported functional relationship between the GABAergic and cholinergic systems in the human central nervous system we have investigated whether there are changes in the GABA(A) and muscarinic receptors in the cortex of subjects from APD-treated subjects with schizophrenia and whether changes were different in subjects who had also received benzodiazepine treatment. We failed to show any strong correlations between changes in GABA(A) and muscarinic receptors in the CNS of subjects with schizophrenia. We showed that subjects with schizophrenia treated with benzodiazepines had lower levels of muscarinic receptors; which was not the case in rats treated with APDs, benzodiazepines or a combination of both drugs. Further, the benzodiazepine binding site, but not the muscimol binding site, was decreased in the parietal cortex of subjects with schizophrenia independent of benzodiazepine status at death. These data would therefore support our previously stated hypotheses that changes in the cortical cholinergic and GABAergic systems are involved in the pathophysiology of schizophrenia.
authors.affiliation: The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Parkville, Australia.
authors.forename: Mark C
authors.initials: MC
authors.lastname: McLeod
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scarr
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000493:pharmacokinetics; D018682:GABA Agents / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D009118:Muscimol / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014316:Tritium; D055815:Young Adult
chemical_list: D018682:GABA Agents; D018727:Muscarinic Antagonists; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D014316:Tritium; D001569:Benzodiazepines; D009118:Muscimol; D010890:Pirenzepine; D005442:Flumazenil