Nicotine attenuates place aversion induced by naloxone in single-dose, morphine-treated rats

Psychopharmacology (Berl). 2004 Feb;171(4):398-404. doi: 10.1007/s00213-003-1595-7. Epub 2003 Sep 10.


Rationale: Acute physical dependence refers to the withdrawal syndrome precipitated by an opioid antagonist administered several hours after either a single dose or a short-term infusion of an opioid agonist.

Objectives: We examined the mechanism of nicotine-induced attenuation of naloxone-precipitated withdrawal syndrome when used to produce an aversive motivational state in a place-conditioning paradigm.

Methods: The effect of nicotine was investigated through place aversion induced by naloxone in morphine-pretreated rats. Additionally, the mechanism of nicotine action in this model was explored specifically in relation to the dopaminergic system through the use of dopamine receptor antagonist and agonist.

Results: Place avoidance behavior was potently elicited by naloxone (0.5 mg/kg s.c.) 24 h after a single exposure to morphine (10 mg/kg s.c.). Avoidance behavior was attenuated by pretreatment with a 0.2-mg/kg dose of nicotine 15 min prior to naloxone administration. The effect of nicotine was completely blocked by mecamylamine, but not hexamethonium. The dopamine receptor antagonists haloperidol (0.05, 0.1 mg/kg, s.c.), SCH23390 (0.1 mg/kg, s.c.), raclopride (1.0 mg/kg, s.c.) and eticlopride (0.1 mg/kg, s.c.) showed effects similar to mecamylamine. Additionally, the dopamine receptor agonist apomorphine (0.03, 0.1, 0.3 mg/kg, s.c.) inhibited naloxone-induced place aversion in morphine-treated rats.

Conclusion: The inhibitory effect of nicotine on place aversion induced by naloxone-precipitated morphine withdrawal may involve a dopaminergic portion of the central nervous system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Avoidance Learning / physiology
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Male
  • Morphine / administration & dosage*
  • Naloxone / antagonists & inhibitors
  • Naloxone / pharmacology*
  • Nicotine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Naloxone
  • Nicotine
  • Morphine