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Sex and chronic stress differentially alter phosphorylated mu and delta opioid receptor levels in the rat hippocampus following oxycodone conditioned place preference.

TitleSex and chronic stress differentially alter phosphorylated mu and delta opioid receptor levels in the rat hippocampus following oxycodone conditioned place preference.
Publication TypeJournal Article
Year of Publication2019
AuthorsBellamy JR, Rubin BR, Zverovich A, Zhou Y, Contoreggi NH, Gray JD, McEwen BS, Kreek MJeanne, Milner TA
JournalNeurosci Lett
Volume713
Pagination134514
Date Published2019 Nov 20
ISSN1872-7972
Abstract

Following oxycodone conditioned place preference (CPP) in naïve female and male Sprague Dawley rats, delta- and mu-opioid receptors (DORs and MORs) redistribute in hippocampal CA3 pyramidal cells and GABAergic interneurons in a manner that would promote opioid-associative learning processes, particularly in females. MORs and DORs similarly redistribute in CA3 and hilar neurons following chronic immobilization stress (CIS) in females, but not males, essentially "priming" the opioid system for oxycodone-associative learning. Following CIS, only females acquire oxycodone CPP. The present study determined whether sex and CIS differentially affect the levels of phosphorylated MORs and DORs (pMORs and pDORs) in the hippocampus following oxycodone CPP as phosphorylation is important for opioid receptor internationalization and trafficking. In naïve oxycodone-injected (Oxy) female rats, the density of pMOR-immunoreactivity (ir) was increased in CA1 stratum oriens and CA3a,b strata lucidum and radiatum compared to saline-injected (Sal)-females. Additionally, the density of pDOR-ir increased in the pyramidal cell layer and stratum radiatum of CA2/3a in Oxy-males compared to Sal-males. In CIS females that acquire CPP, pDOR-ir levels were increased in the CA2/3a. These findings indicate only rats that acquire oxycodone CPP have activated MORs and DORs in the hippocampus but that the subregion containing activated opioid receptors differs in females and males. These results are consistent with previously observed sex differences in the hippocampal opioid system following Oxy-CPP.

DOI10.1016/j.neulet.2019.134514
Alternate JournalNeurosci. Lett.
PubMed ID31560995
Grant ListR01 HL136520 / HL / NHLBI NIH HHS / United States