Estrogen Rapidly Attenuates a GABAB Response in Hypothalamic Neurons

Andre H. Lagrange, Edward J. Wagner, Oline K. RØnnekleiv, Martin J. Kelly

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

GABA is a predominant neurotransmitter in the hypothalamus and an important regulator of hypothalamic function. To elucidate the cellular basis for GABAergic action in this region, we used intracellular recordings from identified hypothalamic neurons. Ninety-three percent of the mediobasal hypothalamic neurons responded to GABAB receptor stimulation, and the presence of bicuculline-sensitive synaptic potentials indicated a tonic, GABAA receptor-mediated input. Stimulation of GABAB receptors hyperpolarized these cells by activating an inwardly rectifying potassium conductance. We characterized GABAB responses by generating concentration-response curves to the GABAB agonist baclofen. There was heterogeneity in the responses to baclofen, with one third of the cells having low baclofen potency (EC50 = 5.0 μM). Two thirds of the neurons had a 4-fold higher potency (EC50 = 1.2 μM), larger somas and a more lateral distribution. Previous work has shown that hypothalamic GABAB and μ-opioid receptors open the same K+ channels and that the response to μ-opioid agonists is rapidly attenuated by 17γ-estradiol (E2). In order to test the hypothesis that the coupling of GABAB receptors to K+ channels is also altered, baclofen concentration-response curves were generated before and after an E2 challenge (100 nM, 20 min). Consistent with our hypothesis, the potency of baclofen was decreased nearly 4-fold in a subset of the cells that had a high potency response to baclofen. Furthermore, decreased baclofen potency only occurred in those cells in which E2 also altered the μ-opioid responses. Therefore, our findings suggest that a discrete subpopulation of hypothalamic neurons is sensitive to estrogen actions to alter inhibitory transmission. We propose that the alteration of GABAB and µ-opioid input is consistent with estrogen’s rapid inhibition of the reproductive axis.

Original languageEnglish (US)
Pages (from-to)114-123
Number of pages10
JournalNeuroendocrinology
Volume64
Issue number2
DOIs
StatePublished - Jan 1 1996

Keywords

  • Baclofen
  • Electrophysiology
  • Gonadal steroids
  • Opioid peptides
  • Potassium conductance
  • γ-Aminobutyric acid
  • γ-Aminobutyric acid receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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