Estrogen suppresses μ-opioid- and GABA(B)-mediated hyperpolarization of hypothalamic arcuate neurons

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Abstract

The effects of estrogen on the response of hypothalamic arcuate neurons to μ-opioid and GABA(B) agonists were investigated. Intracellular recordings were made from arcuate neurons in slices prepared from ovariectomized guinea pigs that were pretreated with estrogen or vehicle. Estrogen shifted the dose-response curve to the μ-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly- ol) by 3.4-fold; the EC50 for DAMGO was 240 ± 25 nM in estrogen-treated females versus 70 ± 12 nM in the controls. The maximal hyperpolarization induced by DAMGO was equivalent in neurons from both groups. The K(e) for the naloxone antagonism of the DAMGO response was similar in both groups, which would indicate that the affinity of the μ-receptor was unchanged. To explore where in the receptor/G-protein/K+ channel cascade estrogen may be acting to attenuate the μ-opioid-mediated hyperpolarization, the response to the GABA(B) agonist baclofen was also tested. Estrogen treatment also shifted the dose-response curve for the baclofen-induced hyperpolarization by 3.3-fold without altering the maximum hyperpolarization; the EC50 shifted from 11.0 ± 4.0 μM to 36.0 ± 5.0 μM. All of the neurons were identified after linking the intracellular biocytin with streptavidin-FITC, and a subpopulation of cells in both groups were immunoreactive for β-endorphin. We conclude that estrogen decreases the functional coupling of the μ-opioid and GABA(B) receptors to the inwardly rectifying K+ channel possibly through an action on the G-protein.

Original languageEnglish (US)
Pages (from-to)2745-2750
Number of pages6
JournalJournal of Neuroscience
Volume12
Issue number7
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Neuroscience(all)

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