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.

Keywords: GABA_A receptor, Muscarinic receptor, APDs, Benzodiazepine, Cortex, Schizophrenia, Postmortem CNS