title: Effect of chronic ethanol exposure and its withdrawal on the endocannabinoid system.
abstract: The present study investigated the effect of ethanol (EtOH) exposure and its withdrawal on the central endocannabinoid system utilizing an EtOH vapor inhalation model, which is known to produce functional tolerance and dependence to EtOH. Swiss Webster mice (n=24) were exposed to EtOH vapors for 72h. Mice were sacrificed after 72h following EtOH exposure (n=12) and 24h after its withdrawal (n=12). Radioligand binding assays were performed to measure the density of CB(1) receptor and CB(1) receptor agonist-stimulated [(35)S]GTPgammaS binding in crude synaptic membranes isolated from the cortex, hippocampus, striatum and cerebellum. The density of CB(1) receptor was significantly decreased (31-39%) in all the brain regions when compared to the control group. The CB(1) receptor-stimulated G(i/o) protein activation was also found to be decreased (29-40%) in these brain regions of EtOH exposed mice. Recovery of the CB(1) receptor density, in addition to, the CB(1) receptor-mediated G-protein activation was observed after 24h withdrawal from EtOH. The levels of cortical anandamide, which was significantly increased (147%) by EtOH exposure, returned to basal levels after 24h of withdrawal from EtOH exposure. A significant reduction (21%) in the activity of fatty acid amide hydrolase was found in the cortex of EtOH administered mice. Taken together, the neuroadaptation in the EC system may have a potential role in development of tolerance and dependence to EtOH.
authors.affiliation: Department of Analytical Psychopharmacology, New York State Psychiatric Institute, New York, NY, USA. vyaragudri@nki.rfmh.org
authors.forename: K Yaragudri
authors.initials: KY
authors.lastname: Vinod
authors.forename: Ratnakumar
authors.initials: R
authors.lastname: Yalamanchili
authors.forename: Shan
authors.initials: S
authors.lastname: Xie
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Basalingappa L
authors.initials: BL
authors.lastname: Hungund
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D002853:Chromatography, Liquid; D003511:Cyclohexanols / Q000494:pharmacology; D063388:Endocannabinoids; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013462:Sulfur Radioisotopes; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002492:Central Nervous System Depressants; D003511:Cyclohexanols; D063388:Endocannabinoids; D000431:Ethanol; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D013462:Sulfur Radioisotopes; D000099252:Fatty Acid Amide Hydrolases; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C078814:anandamide