title: Characterization of neonatal rat morphine tolerance and dependence.
abstract: The administration of morphine and fentanyl by continuous intravenous infusion has been shown to produce analgesic tolerance and physical dependence in human neonates. In animals, daily repeated morphine bolus injections is a common method of inducing neonatal rat tolerance and dependence. Yet this method differs from the intravenous route reported to affect human neonates. Alzet osmotic minipumps were implanted in postnatal day 14 rats to provide a continuous morphine infusion more closely mimicking the clinical picture. Rats remained naive or were infused with saline or morphine (0.7 mg/kg/h) for 72 h. Morphine's antinociceptive potency was similar between naive and saline-infused animals, while morphine-infused animals were tolerant. Gender did not contribute to the degree of tolerance observed. Naloxone precipitated withdrawal in the morphine pump-implanted rats was similar to that reported by others. Thus, minipumps provide a useful model for assessing the tolerance and dependence liability of different opioids.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298-0613, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Thornton
authors.forename: A F
authors.initials: AF
authors.lastname: Wang
authors.forename: F L
authors.initials: FL
authors.lastname: Smith
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004343:Drug Implants; D004361:Drug Tolerance; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012737:Sex Factors; D013375:Substance Withdrawal Syndrome / Q000523:psychology
chemical_list: D000701:Analgesics, Opioid; D004343:Drug Implants; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine