Involvement of the beta-endorphin neurons of the hypothalamic arcuate nucleus in ethanol-induced place preference conditioning in mice.
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 2 g/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.
Area de Psicobiología, Universitat Jaume I, Castellón, Spain. raul.pastor@uji.es
Raúl
R
Pastor
Laura
L
Font
Marta
M
Miquel
Tamara J
TJ
Phillips
Carlos M G
CM
Aragon
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D023421:Models, Animal; D009271:Naltrexone / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D001615:beta-Endorphin / Q000378:metabolism*
D000431:Ethanol; D004958:Estradiol; D009271:Naltrexone; D001615:beta-Endorphin; D003345:Corticosterone