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Chronic ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic plasma membrane
B S Basavarajappa1, T B Cooper, B L Hungund
1Division of Analytical Psychopharmacology, New York State Psychiatric Institute, New York, NY 10032, USA.
Brain Research
|June 19, 1998
Summary
Chronic ethanol consumption significantly reduces cannabinoid receptor 1 (CB1) levels in mouse brain membranes without altering receptor affinity. This downregulation suggests a role for CB1 receptors in alcohol tolerance and dependence.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Chronic ethanol (EtOH) consumption impacts the central nervous system by altering biological membranes and receptor functions.
- Cannabinoid receptors (CB1) are implicated in various neurological processes.
Purpose of the Study:
- To investigate the effects of chronic ethanol exposure on cannabinoid receptor 1 (CB1) density and function in mouse brain synaptic plasma membranes (SPM).
Main Methods:
- Synaptic plasma membranes (SPM) were isolated from the brains of mice chronically exposed to ethanol via inhalation for 4 days.
- Radioligand binding assays using [3H]CP55,940 were performed to quantify CB1 receptor levels, affinity, and dissociation kinetics.
- Competition studies with anandamide and Hill transformation analysis were conducted.
Main Results:
- Chronic ethanol exposure led to a significant 58% decrease in CB1 receptor density (Bmax) in mouse brain SPM.
- Receptor affinity (Kd) and the Hill coefficient (nH) remained unchanged, indicating a single class of CB1 receptors.
- Dissociation rate constant (K-1) significantly decreased, and Ki values for anandamide were reduced in the ethanol-exposed group.
Conclusions:
- Chronic ethanol consumption down-regulates CB1 receptors in the mouse brain.
- The observed CB1 receptor downregulation may contribute to the development of alcohol tolerance and dependence.