title: Endocannabinoid/GABA interactions in the entopeduncular nucleus modulates alcohol intake in rats.
abstract: Alcohol use disorder is a compulsive behavior driven by motivational systems and by a poor control of consummatory behavior. The entopeduncular nucleus (EP) seems to be involved in the regulation of executive mechanisms, hence, in the expression of behavior. Endocannabinoids (eCB) are involved in alcohol intake mechanisms. The eCB receptor name cannabinoid receptor 1 (CB1R) is expressed in the EP in GABAergic terminals. The role of the eCB system (eCBs) of the EP in the modulation of alcohol seeking and intake behavior is unknown. Therefore, we decided to investigate the role of the eCBs and its interaction with GABA transmission in rat EP, in the regulation of alcohol intake behavior. Rats were submitted to a 10-day period of moderate alcohol (10% in tap water) ingestion. No tap water was available. On day 11, either anandamide (AEA, CB1 receptor agonist), AM251 (CB1R inverse agonist), baclofen (BAC, GABAB receptor agonist), or CGP35348 (GABAB receptor antagonist) was administered into the EP. One bottle of water and one of alcohol (10% in water) were available ad libitum for the following 24 h, and consumption was quantified at the end of this period. Results show that administration of AEA into the EP decreased alcohol consumption while AM251 and BAC administered independently increased alcohol consumption. AEA prevented the increase induced by AM251 or BAC. Likewise, CGP35348 prevented alcohol ingestion induced by AM251. These data suggest that eCBs dysfunction in the EP may be playing a crucial role in the abuse and dependence of alcohol and other drugs.
authors.affiliation: Grupo de Neurociencias, Laboratorio de Canabinoides, Depto. de Fisiología, Universidad Nacional Autónoma de México, Apdo. Postal 70-250, México, D.F. 04510, Mexico. mendezm@unam.mx
authors.forename: Mónica
authors.initials: M
authors.lastname: Méndez-Díaz
authors.forename: Seraid
authors.initials: S
authors.lastname: Caynas Rojas
authors.forename: David
authors.initials: D
authors.lastname: Gómez Armas
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: Ruiz-Contreras
authors.forename: Raúl
authors.initials: R
authors.lastname: Aguilar-Roblero
authors.forename: Oscar
authors.initials: O
authors.lastname: Prospéro-García
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism*; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000378:metabolism*; D018755:GABA Agonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D018755:GABA Agonists; D018756:GABA Antagonists; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid