Genetic dissociation of two behaviors associated with nicotine addiction: beta-2 containing nicotinic receptors are involved in nicotine reinforcement but not in withdrawal syndrome

Psychopharmacology (Berl). 2006 Aug;187(2):189-99. doi: 10.1007/s00213-006-0418-z. Epub 2006 Jun 3.


Rationale: Nicotine addiction is characterized by two distinct behaviors, chronic compulsive self-administration and the induction of a withdrawal syndrome upon cessation of nicotine consumption.

Objective: To examine if these two processes rely on beta2-containing nicotinic receptors--beta2*nAChRs--we analyzed the behavior of mice lacking these receptors in the two situations.

Results: First, we showed that, in contrast to wild-type (WT) mice, beta2-knockout (beta2-/-) mice exhibit no intra-ventral tegmental area (VTA) nicotine self-administration, whereas their ability to self-administer morphine is intact. However, beta2-/- mice showed some sensitivity to locomotor effects of nicotine, implying an effect of the drug on other nicotinic subtypes. Then, we observed that beta2-/- mice exhibited a normal nicotine withdrawal syndrome, i.e., increased levels of rearing and jumping upon precipitated withdrawal. Thus, the beta2*nAChRs are not involved in the behaviors induced by cessation of nicotine consumption.

Conclusion: Taken together, the present data demonstrated a genetic dissociation of two distinct behavioral patterns associated with nicotine addiction. They further suggested that independent molecular mechanisms underlie these two aspects, offering the possibility of controlling them separately.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphine / administration & dosage
  • Nicotine / administration & dosage
  • Nicotine / toxicity*
  • Receptors, Nicotinic / genetics*
  • Reinforcement, Psychology*
  • Self Administration
  • Substance Withdrawal Syndrome / genetics*
  • Tobacco Use Disorder / genetics*
  • Ventral Tegmental Area / drug effects


  • Receptors, Nicotinic
  • nicotinic receptor beta2
  • Nicotine
  • Morphine