Feil Family Brain & Mind Research Institute

You are here

Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress.

TitleSex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress.
Publication TypeJournal Article
Year of Publication2016
AuthorsMazid S, Hall BS, Odell SC, Stafford K, Dyer AD, Van Kempen TA, Selegean J, McEwen BS, Waters EM, Milner TA
JournalNeurobiol Stress
Volume5
Pagination37-53
Date Published2016 Dec
ISSN2352-2895
Abstract

Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs). Immediately after acute immobilization stress (AIS) or one-day after chronic immobilization stress (CIS), the brains of adult female and male rats were perfusion-fixed with aldehydes. The CA3b region and the dentate hilus of the dorsal hippocampus were quantitatively analyzed by light microscopy using DOR immunoperoxidase or dual label electron microscopy for DOR using silver intensified immunogold particles (SIG) and GABA using immunoperoxidase. At baseline, females compared to males had more DORs near the plasmalemma of pyramidal cell dendrites and about 3 times more DOR-labeled CA3 dendritic spines contacted by mossy fibers. In AIS females, near-plasmalemmal DOR-SIGs decreased in GABAergic hilar dendrites. However, in AIS males, near-plasmalemmal DOR-SIGs increased in CA3 pyramidal cell and hilar GABAergic dendrites and the percentage of CA3 dendritic spines contacted by mossy fibers increased to about half that seen in unstressed females. Conversely, after CIS, near-plasmalemmal DOR-SIGs increased in hilar GABA-labeled dendrites of females whereas in males plasmalemmal DOR-SIGs decreased in CA3 pyramidal cell dendrites and near-plasmalemmal DOR-SIGs decreased hilar GABA-labeled dendrites. As CIS in females, but not males, redistributed DOR-SIGs near the plasmalemmal of hilar GABAergic dendrites, a subsequent experiment examined the acute affect of oxycodone on the redistribution of DOR-SIGs in a separate cohort of CIS females. Plasmalemmal DOR-SIGs were significantly elevated on hilar interneuron dendrites one-hour after oxycodone (3 mg/kg, I.P.) administration compared to saline administration in CIS females. These data indicate that DORs redistribute within CA3 pyramidal cells and dentate hilar GABAergic interneurons in a sexually dimorphic manner that would promote activation and drug related learning in males after AIS and in females after CIS.

DOI10.1016/j.ynstr.2016.11.002
Alternate JournalNeurobiol Stress
PubMed ID27981195
PubMed Central IDPMC5145913
Grant ListT32 DA007274 / DA / NIDA NIH HHS / United States
R21 AG039850 / AG / NIA NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL098351 / HL / NHLBI NIH HHS / United States
P01 AG016765 / AG / NIA NIH HHS / United States
P01 HL096571 / HL / NHLBI NIH HHS / United States