Prevention of morphine discontinuation phenomenon in mice by ondansetron, a selective 5-HT3 antagonist.
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.
Roychoudhury
M
M
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000517:prevention & control*; D009294:Narcotics / Q000494:pharmacology*; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy; D011985:Receptors, Serotonin / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D000701:Analgesics, Opioid; D009294:Narcotics; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D009020:Morphine