Effects of benzodiazepine treatment on cortical GABA(A) and muscarinic receptors: Studies in schizophrenia and rats.
Summary of "Effects of benzodiazepine treatment on cortical GABA(A) and muscarinic receptors: Studies in schizophrenia and rats."
Changes in cortical gamma-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.
Affiliation
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Parkville, Australia; The Department of Psychiatry, The University of Melbourne, Victoria, Australia.
Journal Details
This article was published in the following journal.
Name: Psychiatry research
ISSN: 0165-1781
Pages: 139-46
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20483174
- DOI: http://dx.doi.org/10.1016/j.psychres.2009.03.034
Medical and Biotech [MESH] Definitions
Baclofen
A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist at GABA-B receptors (RECEPTORS, GABA-B). It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.
Receptors, Gaba-a
Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and control an integral membrane chloride channel. GABA-A receptors are the most prevalent inhibitory neurotransmitter receptors in the brain. Several isoforms have been cloned, and they belong to a superfamily which includes nicotinic receptors, glycine receptors, and 5HT-3 receptors. Most GABA-A receptors have separate modulatory sites sensitive to benzodiazepines and to barbiturates.
Muscarinic Antagonists
Drugs that bind to but do not activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC), thereby blocking the actions of endogenous acetylcholine or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. Antagonists that discriminate among the various muscarinic receptor subtypes and might allow better control of peripheral and central actions are under development.
Muscarinic Agonists
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
Gaba Agonists
Drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
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