Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal

Marc R. Azar, Byron Jones, Gery Schulteis

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Abstract

Rationale: Conditioned place aversion (CPA) is known to be a sensitive measure of the aversive motivational state produced by opioid withdrawal in rats made chronically dependent on opioids. Objective: The purpose of the present study was to examine the sensitivity of the CPA model in detecting a possible aversive state associated with naloxone-precipitated withdrawal from acute treatment with morphine. Methods: Doses of morphine and naloxone, as well as number of conditioning trials, were systematically varied to determine the minimum conditions that would result in a detectable CPA in male Wistar rats. Naloxone (0.003-16.7 mg/kg) was administered 4 h after an injection of vehicle or morphine (1.0, 3.3, or 5.6 mg/kg) and immediately prior to confinement to one compartment of the conditioning apparatus; rats received either one or two such naloxone-conditioning trials (separate by 48 h). Results: Morphine (5.6 mg/kg) followed 4 h later by vehicle produced no significant preference or aversion. In morphine-naive rats, 10 mg/kg naloxone was required to produce a significant CPA with two cycles of conditioning. When increasing doses of morphine were administered (1.0, 3.3, 5.6 mg/kg), significant increases in naloxone potency to elicit a CPA were observed (16-, 211-, and 1018-fold potency shifts, respectively). Naloxone potency after two pretreatments with 5. 6 mg/kg morphine was comparable to its potency to elicit a CPA after chronic exposure to morphine. Although naloxone was still effective in producing a CPA after a single conditioning cycle (and hence a single morphine exposure), its effects were dramatically reduced relative to those seen with two conditioning cycles. Conclusions: CPA is a reliable and sensitive index of the aversive motivational state accompanying withdrawal from acute opioid dependence.

Original languageEnglish (US)
Pages (from-to)42-50
Number of pages9
JournalPsychopharmacology
Volume170
Issue number1
DOIs
StatePublished - Oct 1 2003

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Morphine
Opioid Analgesics
Naloxone
Wistar Rats
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal. / Azar, Marc R.; Jones, Byron; Schulteis, Gery.

In: Psychopharmacology, Vol. 170, No. 1, 01.10.2003, p. 42-50.

Research output: Contribution to journalArticle

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