Effect of the μ-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice

Robert M. Slugg, Michael D. Hayward, Oline K. Rønnekleiv, Malcolm J. Low, Martin J. Kelly

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The endogenous opioid neurotransmitter β-endorphin (β-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any β-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia. To further understand the cellular bases of these responses, we have studied medio-basal hypothalamic (MBH) neurons, including POMC neurons, using whole-cell patch recording in an in vitro slice preparation. Twenty-seven MBH cells were recorded in wild-type and 25 MBH cells were recorded in β-END knockout mice. Neurons from both genotypes showed a significant positive correlation between DAMGO concentration (from 30 nM to 10 μM) and the induced outward K+ current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC50, or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing 3H-DAMGO did not reveal any differences in total μ-opioid receptor binding between genotypes. Therefore, we conclude that the complete absence of β-END throughout development did not alter either the expression of μ-opioid receptors or their coupling to K+ channels in MBH neurons. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)208-217
Number of pages10
JournalNeuroendocrinology
Volume72
Issue number4
DOIs
StatePublished - 2000

Keywords

  • Beta-endorphin
  • Immunocytochemistry
  • K channels
  • Mouse
  • Opioid peptide agonists
  • Opioid peptides
  • Proopiomelanocortin

ASJC Scopus subject areas

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

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