Effects of varenicline and mecamylamine on the acquisition, expression, and reinstatement of nicotine-conditioned place preference by drug priming in rats

Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr;381(4):361-70. doi: 10.1007/s00210-010-0498-5. Epub 2010 Mar 10.


Nicotine addiction is a chronic disorder characterized by a relatively high rate of relapse even after long period of abstinence. In the present study, we used the conditioned place preference (CPP) paradigm to investigate the establishment, extinction, reinstatement, and cross-reinstatement of nicotine-induced place conditioning in rats. First, we revealed that nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.175 mg/kg, base, intraperitoneally (i.p.)). Once established, nicotine CPP was extinguished by repeated testing. Following this extinction phase, nicotine-experienced rats were challenged with nicotine (0.175 mg/kg, i.p.) or morphine (10 mg/kg, i.p.). These priming injections of both drugs induced a marked preference for the compartment previously paired with nicotine. Furthermore, given the important role of alpha4beta2 (a4b2) nicotinic receptor subtype in the acquisition and maintenance of nicotine dependence, we evaluated and compared the efficacy of varenicline, a partial a4b2 nicotinic receptor agonist (0.5, 1, and 2 mg/kg, subcutaneously (s.c.)), and mecamylamine (0.5, 1, and 2 mg/kg, s.c.), a non-selective nicotinic receptor antagonist, in blocking nicotine-induced CPP as well as reinstatement of nicotine CPP provoked by nicotine and morphine. It was shown that both nicotinic receptor ligands attenuated the acquisition and expression of nicotine CPP as well as the expression of reinstatement of nicotine CPP provoked by both drugs. Our results indicate similar cholinergic mechanisms, probably through the a4b2 receptors involved in the rewarding effects of nicotine and morphine in rats and may suggest that nicotinic receptors could be a potential target for developing pharmacotherapeutic strategies to treat and prevent nicotine and/or opioid addiction and relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology
  • Conditioning, Classical / drug effects
  • Dose-Response Relationship, Drug
  • Male
  • Mecamylamine / administration & dosage
  • Mecamylamine / pharmacology
  • Morphine / administration & dosage
  • Morphine / pharmacology
  • Nicotine / administration & dosage*
  • Nicotine / pharmacology
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Antagonists / administration & dosage
  • Nicotinic Antagonists / pharmacology*
  • Quinoxalines / administration & dosage
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Reward
  • Tobacco Use Disorder / physiopathology
  • Varenicline


  • Benzazepines
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Quinoxalines
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • Mecamylamine
  • Nicotine
  • Morphine
  • Varenicline