Involvement of the beta-endorphin neurons of the hypothalamic arcuate nucleus in ethanol-induced place preference conditioning in mice

Raúl Pastor, Laura Font, Marta Miquel, Tamara J. Phillips, Carlos M.G. Aragon

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: Increasing evidence indicates that mu- and delta-opioid receptors are decisively involved in the retrieval of memories underlying conditioned effects of ethanol. The precise mechanism by which these receptors participate in such effects remains unclear. Given the important role of the proopiomelanocortin (POMc)-derived opioid peptide beta-endorphin, an endogenous mu- and delta-opioid receptor agonist, in some of the behavioral effects of ethanol, we hypothesized that beta-endorphin would also be involved in ethanol conditioning. Methods: In this study, we treated female Swiss mice with estradiol valerate (EV), which induces a neurotoxic lesion of the beta-endorphin neurons of the hypothalamic arcuate nucleus (ArcN). These mice were compared to saline-treated controls to investigate the role of beta-endorphin in the acquisition, extinction, and reinstatement of ethanol (0 or 2g/kg; intraperitoneally)-induced conditioned place preference (CPP). Results: Immunohistochemical analyses confirmed a decreased number of POMc-containing neurons of the ArcN with EV treatment. EV did not affect the acquisition or reinstatement of ethanol-induced CPP, but facilitated its extinction. Behavioral sensitization to ethanol, seen during the conditioning days, was not present in EV-treated animals. Conclusions: The present data suggest that ArcN beta-endorphins are involved in the retrieval of conditioned memories of ethanol and are implicated in the processes that underlie extinction of ethanol-cue associations. Results also reveal a dissociated neurobiology supporting behavioral sensitization to ethanol and its conditioning properties, as a beta-endorphin deficit affected sensitization to ethanol, while leaving acquisition and reinstatement of ethanol-induced CPP unaffected.

Original languageEnglish (US)
Pages (from-to)2019-2029
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Beta-endorphin
  • Conditioned place preference
  • Ethanol
  • Extinction
  • Naltrexone

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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