Alcohol reinstatement after prolonged abstinence from alcohol drinking by female adolescent rats: Roles of cyclooxygenase-2 and the prostaglandin E 2 receptor 1.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Kline HL;Kline HL;Kline HL; Yamamoto BK; Yamamoto BK; Yamamoto BK
  • Source:
    Drug and alcohol dependence [Drug Alcohol Depend] 2022 Jul 01; Vol. 236, pp. 109491. Date of Electronic Publication: 2022 May 06.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Ireland NLM ID: 7513587 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0046 (Electronic) Linking ISSN: 03768716 NLM ISO Abbreviation: Drug Alcohol Depend Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier
      Original Publication: Lausanne, Elsevier Sequoia.
    • Subject Terms:
      Alcohol Drinking*/metabolism ; Receptors, Prostaglandin E, EP1 Subtype*; Cyclooxygenase 2/*metabolism; Adolescent ; Animals ; Ethanol ; Female ; Humans ; Prostaglandins E ; Rats
    • 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 E 2 (PGE 2 ) in the brain and the role of COX-2 and PGE 2 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 PGE 2 content. The PGE 2 receptor 1 (EP 1 ) 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 PGE 2 150.5 ± 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.
      (Copyright © 2022 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Adolescent; Alcohol; COX-2; Female; PGE(2); Reinstatement
    • Accession Number:
      0 (Prostaglandins E)
      0 (Ptger1 protein, rat)
      0 (Receptors, Prostaglandin E, EP1 Subtype)
      3K9958V90M (Ethanol)
      EC 1.14.99.1 (Cyclooxygenase 2)
    • Publication Date:
      Date Created: 20220510 Date Completed: 20220617 Latest Revision: 20220922
    • Publication Date:
      20240105
    • Accession Number:
      10.1016/j.drugalcdep.2022.109491
    • Accession Number:
      35537317