The interaction of morphine and γ-aminobutyric acid (GABA)ergic systems in anxiolytic behavior: Using μ-opioid receptor knockout mice

Kenroh Sasaki, Lir Wan Fan, Lu Tai Tien, Tangeng Ma, Horace H. Loh, Ing K. Ho

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

We investigated the interaction of morphine and γ-aminobutyric acid (GABA)ergic systems in anxiolytic action using μ-opioid receptor knockout and wild-type female mice. An elevated plus-maze test was used to assess anxiolytic behavior. The anxiolytic activities were monitored after experimental animals were pretreated with morphine [15 mg/kg, subcutaneous (s.c.)] and 3 h later received a single dose of muscimol (0.5 mg/kg, s.c.). In another experiment, mice received a single dose of opioid antagonist, naloxone [1.0 mg/kg, intraperitoneal (i.p.)], or GABAA receptor antagonist, (+)bicucullin (2.0 mg/kg, i.p.), 2.5 h after the morphine and 30 min before the muscimol injection. Control mice received vehicle only. The results show that morphine enhanced muscimol-induced staying time in open arms by 160% in wild-type mice. Moreover, the effect of morphine in the wild type was inhibited by the pretreatment of either naloxone or (+)bicucullin. Autoradiographic analysis indicated that morphine-administration raised [3H]muscimol binding by around 25% of the basal level in posterior thalamic, mediodorsal thalamic, and amygdaloid areas, but not in the hippocampal area in wild-type mice. In contrast, morphine administration did not alter the [3H]muscimol binding in μ-opioid receptor knockout mice. The present results reveal that μ-opioid receptor may play a role in the modification of anxiolytic behavior regulated by GABAergic neurotransmission.

Original languageEnglish (US)
Pages (from-to)689-694
Number of pages6
JournalBrain Research Bulletin
Volume57
Issue number5
DOIs
StatePublished - Mar 15 2002

Keywords

  • Anxiolytic behavior
  • Autoradiography
  • Elevated plus-maze
  • Muscimol
  • μ-Opioid receptor knockout mice

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