Autoradiographic analysis of GABAA receptors in μ-opioid receptor knockout mice

Lu Tai Tien, Tangeng Ma, Lir Wan Fan, Horace H Loh, Ing Kang Ho

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Anatomical evidence indicates that γ-aminobutyric acid (GABA)-ergic and opioidergic systems are closely linked and act on the same neurons. However, the regulatory mechanisms between GABAergic and opioidergic system have not been well characterized. In the present study, we investigated whether there are changes in GABAA receptors in mice lacking μ-opioid receptor gene. The GABAA receptor binding was carried out by autoradiography using [3H]-muscimol (GABAA), [3H]-flunitrazepam (FNZ, native type 1 benzodiazepine) and [35S]-t- butylbicyclophosphorothionate (TBPS, binding to GABAA-gated chloride channels) in brain slices of wild type and μ-opioid receptor knockout mice. The binding of [3H]-FNZ in μ-opioid receptor knockout mice was significantly higher than that of the wild type controls in most of the cortex and hippocampal CA1 and CA2 formations. μ-Opioid receptor knockout mice show significantly lower binding of [35S]-TBPS than that of the wild type mice in few of the cortical areas including ectorhinal cortex layers I, III, and V, but not in the hippocampus. There was no significant difference in binding of [3H]-muscimol between μ-opioid receptor knockout and wild type mice in the cortex and hippocampus. These data indicate that there are specific regional changes in GABAA receptor binding sites in μ-opioid receptor knockout mice. These data also suggest that there are compensatory up-regulation of benzodiazepine binding site of GABAA receptors in the cortex and hippocampus and down-regulation of GABA-gated chloride channel binding site of GABAA receptors in the cortex of the μ-opioid receptor knockout mice.

Original languageEnglish (US)
Pages (from-to)1891-1897
Number of pages7
JournalNeurochemical Research
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2007

Keywords

  • Autoradiography
  • [ S]-t-Butylbicyclophosphorothionate
  • [H]-Flunitrazepam
  • [H]-Muscimol
  • μ-Opioid receptor knockout mice

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