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.
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Parkville, Australia; The Department of Psychiatry, The University of Melbourne, Victoria, Australia.
This article was published in the following journal.
Name: Psychiatry research
- 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
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.
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.
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.
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.
Drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
Hypnotic zolpidem is a positive allosteric modulator of γ-aminobutyric acid (GABA) action, with preferential although not exclusive binding for α1 subunit-containing GABA(A) receptors. The pharmacol...
Zolpidem, a widely used hypnotic drug which acts through benzodiazepine binding sites, is a positive allosteric modulator of gamma-aminobutyric acid (GABA) action with preferential affinity for GABA(A...
Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for treating anxiety or nervousness, Generalized Anxiety Disorder (GAD), symptoms of opiate withdrawal, insomnia, neuralgia, co...
Importance of the field: Positive allosteric modulators of GABA(B) receptors may have a similar potential as positive modulators of GABA(A) receptors, the benzodiazepines discovered in 1957. The disco...
These studies were undertaken to investigate the selectivity of cortical muscarinic receptor radioligand binding in muscarinic M1 and M4 receptor knockout mice and to determine whether a marked decrea...
The goal of this series of challenge studies is to examine the impact of menstrual cycle phase on cortical GABA response to administration of agents with either direct (benzodiazepines) or...
The purpose of this protocol is to measure peripheral benzodiazepine receptors in the brain using positron emission tomography (PET) and compare the imaging results between patients and he...
Disturbances in the amino acid neurotransmitter (AANt), gamma-amino butyric acid (GABA) function are hypothesized to contribute to the neurobiology of Major Depressive Disorder (MDD) and i...
The purpose of this study is to determine the way by which Alprazolam (Xanax) an anti-anxiety drug affects specialized molecules in your brain called GABA (A) receptors that alter your bod...
The purpose this study is to measure cortical gama-aminobutyric acid levels (GABA) levels in menopausal women with major depressive disorder and healthy subjects using nuclear magnetic res...