Alcohol reinstatement after prolonged abstinence from alcohol drinking by female adolescent rats: Roles of cyclooxygenase-2 and the prostaglandin E2 receptor 1. (1st July 2022)

• Record Type: Journal Article
• Authors: Kline, Hannah L.; Yamamoto, Bryan K.
• Is Part Of: Drug and alcohol dependence. Volume 236(2022)
• Publication Date: 2022-07-01
• Subjects: BAC Blood Alcohol Content -- COX-2 Cyclooxygenase-2 -- ET-1 endothelin-1 -- EtOH ethanol -- DMSO dimethyl sulfoxide -- PD postnatal day -- PGE2 prostaglandin E2 -- EP1 receptor prostaglandin E2 receptor 1 -- SC-51089 8-chloro-2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide-dibenz[b, f][1, 4]oxazepine-10(11 H)-carboxylic acid, monohydrochloride -- H2O water; Alcohol -- Reinstatement -- Adolescent -- Female -- COX-2 -- PGE2; Drug abuse -- Periodicals; Alcoholism -- Periodicals; 616.86
• DOI: 10.1016/j.drugalcdep.2022.109491
• Languages: English
• ISSNs: 0376-8716

Abstract

Abstract: Background: Adolescent alcohol misuse is a global problem that can significantly increase the reinstatement of alcohol drinking during re-exposure after abstinence, but the mechanism that causes this increase is unknown. Female adolescents are an understudied population but they are particularly vulnerable to adolescent-onset alcohol abuse. We aimed to determine how adolescent-onset alcohol drinking affects pro-inflammatory mediators endothelin-1 (ET-1), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2 ) in the brain and the role of COX-2 and PGE2 in EtOH reinstatement in adolescent females. Methods: Adolescent female rats were exposed to a 2-bottle choice paradigm of water vs 5% ethanol (EtOH) every other day over a 21 day period. ET-1 and COX-2 proteins were measured in the dorsal striatum (DS) after a 4 week abstinence from EtOH drinking. The COX-2 inhibitor nimesulide was then administered during abstinence prior to an EtOH reinstatement or sucrose preference or to measure PGE2 content. The PGE2 receptor 1 (EP1 ) antagonist SC-51089 was then administered prior to EtOH reinstatement during which EtOH intake was measured. Results: EtOH drinking significantly increased ET-1 by 33.8 ± 8.9% and COX-2 by 71.4 ± 24.3% in the DS. Treatment with nimesulide during abstinence attenuated EtOH intake during reinstatement after prolonged abstinence by 40.3 ± 12.4% compared to saline controls. Adolescent EtOH drinking and abstinence increased PGE2 150.5 ± 30.9% in the DS and nimesulide attenuated this increase. SC-51089 treatment during abstinence attenuated EtOH reinstatement by 48.1 ± 8.4% compared to DMSO controls. Conclusions: These experiments identified a prostaglandin-mediated mechanism that offers a putative pharmacological target to attenuate EtOH reinstatement after adolescent-onset EtOH drinking. Highlights: Adolescent EtOH drinking increases ET-1 and COX-2 in the adult dorsal striatum. COX-2 inhibition during EtOH abstinence attenuates reinstatement of EtOH intake. Adolescent EtOH increases COX-2-dependent PGE2 in the adult dorsal striatum. PGE2 receptor antagonism during abstinence attenuates reinstatement of EtOH intake.