title: Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress.
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.
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States.
authors.forename: Sanoara
authors.initials: S
authors.lastname: Mazid
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, United States.
authors.forename: Baila S
authors.initials: BS
authors.lastname: Hall
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, United States.
authors.forename: Shannon C
authors.initials: SC
authors.lastname: Odell
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States.
authors.forename: Khalifa
authors.initials: K
authors.lastname: Stafford
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States.
authors.forename: Andreina D
authors.initials: AD
authors.lastname: Dyer
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, United States.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Van Kempen
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States.
authors.forename: Jane
authors.initials: J
authors.lastname: Selegean
authors.affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Waters
authors.affiliation: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, United States; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, United States; Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
keywords: CA3 pyramidal cells; Drug addiction; Electron microscopy; GABAergic interneurons; Neural plasticity; Oxycodone