title: URB597 inhibits oxidative stress induced by alcohol binging in the prefrontal cortex of adolescent rats.
abstract: Heavy episodic drinking (binging), which is highly prevalent among teenagers, results in oxidative damage. Because the prefrontal cortex (PFC) is not completely mature in adolescents, this brain region may be more vulnerable to the effects of alcohol during adolescence. As endocannabinoids may protect the immature PFC from the harmful effects of high doses of alcohol, this study investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on oxidative stress induced by acute or chronic binge alcohol intake in adolescent rats. At 40min after intraperitoneal pre-treatment with URB597 (0.3mg/kg) or vehicle (Veh), ethanol (EtOH; 3 or 6g/kg, intragastrically) or distilled water (DW) was administered in 3 consecutive sessions (acute binging) or 3 consecutive sessions over 4 weeks (chronic binging). Oxidative stress in PFC slices in situ was measured by dihydroethidium fluorescence staining. At the higher EtOH dose (6g/kg), pre-treatment with URB597 significantly reduced (p<0.01) the production of superoxide anions in the PFC after acute (42.8% decrease) and chronic binge EtOH consumption (44.9% decrease) compared with pre-treatment with Veh. As URB597 decreases anandamide metabolism, this evidence shows an antioxidant effect of endocannabinoids to suppress acute and chronic binge alcohol intake-induced oxidative stress in the PFC of adolescent rats.
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil.
authors.forename: Renan
authors.initials: R
authors.lastname: Pelição
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil.
authors.forename: Matheus C
authors.initials: MC
authors.lastname: Santos
authors.affiliation: Department of Physiology and Biophysics, ICB/UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Freitas-Lima
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil.
authors.forename: Silvana S
authors.initials: SS
authors.lastname: Meyrelles
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil.
authors.forename: Elisardo C
authors.initials: EC
authors.lastname: Vasquez
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil.
authors.forename: Ester M
authors.initials: EM
authors.lastname: Nakamura-Palacios
authors.affiliation: Department of Physiological Sciences, CCS/UFES, Vitória, ES, Brazil. Electronic address: livia.melo.rodrigues@gmail.com.
authors.forename: Lívia C M
authors.initials: LC
authors.lastname: Rodrigues
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage*; D063425:Binge Drinking / Q000378:metabolism*; D002219:Carbamates / Q000008:administration & dosage*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D000431:Ethanol; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
keywords: Alcohol; Antioxidant effect; Binge; Oxidative stress; Prefrontal cortex; URB597