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

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.