TY - JOUR
T1 - Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneurons
AU - Torres-Reveron, Annelyn
AU - Williams, Tanya J.
AU - Chapleau, Jeanette D.
AU - Waters, Elizabeth M.
AU - McEwen, Bruce S.
AU - Drake, Carrie T.
AU - Milner, Teresa A.
N1 - Funding Information:
This work was supported by the following grants: DA08259 (TAM; CTD); Minority supplement to DA08259 (ATR); HL18974 (TAM); NS07080 (BSM). We thank Ms. Priya Prasad for her assistance in data collection, Ms. Louisa Thompson for technical assistance and Dr. Joseph P. Pierce for his helpful advice.
PY - 2009/9
Y1 - 2009/9
N2 - The endogenous hippocampal opioid systems are implicated in learning associated with drug use. Recently, we showed that ovarian hormones regulate enkephalin levels in the mossy fiber pathway. This pathway overlaps with parvalbumin (PARV)-basket interneurons that contain the enkephalin-activated mu opioid receptors (MORs) and are important for controlling the "temporal timing" of granule cells. Here, we evaluated the influence of ovarian steroids on the trafficking of MORs in PARV interneurons. Two groups of female rats were analyzed: cycling rats in proestrus (relatively high estrogens) or diestrus; and ovariectomized rats euthanized 6, 24 or 72 h after estradiol benzoate (10 μg, s.c.) administration. Dorsal hippocampal sections were dually immunolabeled for MOR and PARV and examined by light and electron microscopy. As in males, in females MOR-immunoreactivity (-ir) was in numerous PARV-labeled perikarya, dendrites and terminals in the dentate hilar region. Variation in ovarian steroid levels altered the subcellular distribution of MORs in PARV-labeled dendrites but not terminals. In normal cycling rats, MOR-gold particles on the plasma membrane of small PARV-labeled dendrites (area < 1 μm2) had higher density in proestrus rats than in diestrus rats. Likewise, in ovariectomized rats MORs showed higher density on the plasma membrane of small PARV-labeled dendrites 72 h after estradiol exposure. The number of PARV-labeled cells was not affected by estrous cycle phase or estrogen levels. These results demonstrate that estrogen levels positively regulate the availability of MORs on GABAergic interneurons in the dentate gyrus, suggesting cooperative interaction between opioids and estrogens in modulating principal cell excitability.
AB - The endogenous hippocampal opioid systems are implicated in learning associated with drug use. Recently, we showed that ovarian hormones regulate enkephalin levels in the mossy fiber pathway. This pathway overlaps with parvalbumin (PARV)-basket interneurons that contain the enkephalin-activated mu opioid receptors (MORs) and are important for controlling the "temporal timing" of granule cells. Here, we evaluated the influence of ovarian steroids on the trafficking of MORs in PARV interneurons. Two groups of female rats were analyzed: cycling rats in proestrus (relatively high estrogens) or diestrus; and ovariectomized rats euthanized 6, 24 or 72 h after estradiol benzoate (10 μg, s.c.) administration. Dorsal hippocampal sections were dually immunolabeled for MOR and PARV and examined by light and electron microscopy. As in males, in females MOR-immunoreactivity (-ir) was in numerous PARV-labeled perikarya, dendrites and terminals in the dentate hilar region. Variation in ovarian steroid levels altered the subcellular distribution of MORs in PARV-labeled dendrites but not terminals. In normal cycling rats, MOR-gold particles on the plasma membrane of small PARV-labeled dendrites (area < 1 μm2) had higher density in proestrus rats than in diestrus rats. Likewise, in ovariectomized rats MORs showed higher density on the plasma membrane of small PARV-labeled dendrites 72 h after estradiol exposure. The number of PARV-labeled cells was not affected by estrous cycle phase or estrogen levels. These results demonstrate that estrogen levels positively regulate the availability of MORs on GABAergic interneurons in the dentate gyrus, suggesting cooperative interaction between opioids and estrogens in modulating principal cell excitability.
KW - Endogenous opioids
KW - Estrogen
KW - Estrous cycle
KW - Hippocampus
KW - Ovariectomy
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U2 - 10.1016/j.expneurol.2009.06.001
DO - 10.1016/j.expneurol.2009.06.001
M3 - Article
C2 - 19505458
AN - SCOPUS:68549109384
SN - 0014-4886
VL - 219
SP - 319
EP - 327
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -