Prevention of morphine discontinuation phenomenon in mice by ondansetron, a selective 5-HT3 antagonist

Methods Find Exp Clin Pharmacol. 1996 Dec;18(10):677-83.

Abstract

The effects of ondansetron, a highly potent and selective 5-HT3 receptor antagonist, in the prevention of tolerance to and dependence on morphine were studied in mice using a 9-day schedule. Chronic administration of morphine (10 mg/kg i.p. twice daily for 9 days) produced tolerance to the analgesic effects and animals showed withdrawal jumps on day 10 when challenged with naloxone (2 mg/kg). Chronic treatment with ondansetron (0.01 and 0.1 mg/kg) followed by saline on days 1-9 failed to produce any significant change in tail-flick latency in the saline-pretreated group. Repeated administration of ondansetron (0.01 and 0.1 mg/kg) for 9 days, however, attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg). The higher dose of ondansetron (0.1 mg/kg) also suppressed the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal on day 10 of testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Drug Interactions
  • Drug Tolerance
  • Female
  • Male
  • Mice
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Morphine Dependence / prevention & control*
  • Narcotics / pharmacology*
  • Ondansetron / administration & dosage
  • Ondansetron / pharmacology*
  • Pain / drug therapy
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology*
  • Substance Withdrawal Syndrome / drug therapy

Substances

  • Analgesics, Opioid
  • Narcotics
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Ondansetron
  • Morphine