Nicotine-induced conditioned place preference in rats: sex differences and the role of mGluR5 receptors

Neuropharmacology. 2010 Feb;58(2):374-82. doi: 10.1016/j.neuropharm.2009.10.001. Epub 2009 Oct 13.


To elucidate sex differences in nicotine addiction and the underlying mechanisms of the conditioning aspects of nicotine, nicotine-induced conditioned place preference (CPP) was evaluated in male and female Sprague Dawley rats using a three-chambered CPP apparatus and a biased design. In a series of experiments, the dose-response curve was obtained, pairings between the drug and initially non-preferred versus preferred compartments were compared, and the involvement of mGluR5 receptors in nicotine-induced CPP was evaluated. Modulation of nicotine-induced CPP with mGluR5 inhibition was obtained by MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride). Our results show that nicotine induces CPP dose-dependently in male rats but not in female rats. The comparison of the biased protocol, pairing nicotine with the initially preferred and non-preferred chambers, indicated that nicotine-induced CPP in male rats under both conditions, but the effect was stronger when nicotine was paired with the initially non-preferred side. The selective mGluR5 antagonist MPEP inhibited nicotine-induced CPP in male rats. In conclusion, the results of the current study in rats demonstrate that the conditioning effect of nicotine is more important in males than in females. Furthermore, in line with reported findings, our results suggest that mGluR5 antagonism may be therapeutically useful in smoking cessation during the maintenance of smoking behavior when conditioning plays an important role, notwithstanding the fact that this effect is observed only in male rats, not in females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Automation
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Male
  • Neuropsychological Tests
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Reproducibility of Results
  • Sex Characteristics*
  • Space Perception / drug effects*
  • Space Perception / physiology


  • Excitatory Amino Acid Antagonists
  • Grm5 protein, rat
  • Nicotinic Agonists
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Nicotine
  • 6-methyl-2-(phenylethynyl)pyridine