Gabaergic drugs, morphine and morphine tolerance: A study in relation to nociception and gastrointestinal transit in mice

S. P. Sivam, I. K. Ho

Research output: Contribution to journalArticle

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Abstract

Agonists and antagonists of γ-aminobutyric acid, i.e. GABAergic drugs, such as muscimol, badofen or bicuculline, alone or in combination, exhibited analgesic effects per se and enhanced the analgesia induced by morphine. The analgesic effects of GABAergic drugs were unaffected by admini tration of naloxone in a dose which antagonized the analgesia induced by morphine. The ED50 for the antinociceptive effect of muscimol, bicuculline, picrotoxin, gabaculline or aminooxyacetic acid (AOAA) was not affected in the morphine-tolerant group as compared to the control group, in contrast to the increase in the ED50 for morphine under similar conditions; this indicated that there was no development of cross-tolerance between morphine and GABAergic drugs. Muscimol suppressed the abrupt withdrawal-jumping induced by morphine and enhanced the suppression of this phenomenon by morphine. The GABAergic drugs also shared with morphine the property of inhibiting gastrointestinal (GIT) motility. Naloxone reversed the inhibition of motility induced by morphine but failed to influence that induced by GABAergic drugs. In the morphine-tolerant state, the sensitivity of gastrointestinal motility to morphine decreased, whereas, the sensitivity to GABAergic drugs remained unaltered. The results indicate that GABAergic drugs share some of the classical properties of morphine, such as analgesia and inhibition of gastrointestinal motility, but they probably do so by different mechanisms.

Original languageEnglish (US)
Pages (from-to)767-774
Number of pages8
JournalNeuropharmacology
Volume22
Issue number6
DOIs
StatePublished - Jun 1983

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Keywords

  • GABA
  • GABAergic drugs
  • analgesia
  • gastrointestinal transit
  • morphine
  • opiate tolerance

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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