Age-dependent differences in nicotine reward and withdrawal in female mice

Psychopharmacology (Berl). 2008 Jun;198(2):201-10. doi: 10.1007/s00213-008-1117-8. Epub 2008 Mar 13.


Rationale: Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female.

Objective: The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence.

Materials and methods: Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined.

Results: In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature.

Conclusions: These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Aging / psychology*
  • Animals
  • Anxiety / psychology
  • Body Temperature / drug effects
  • Conditioning, Operant / drug effects*
  • Drug Tolerance
  • Female
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Pain Measurement / drug effects
  • Reaction Time / drug effects
  • Reinforcement Schedule
  • Reward
  • Substance Withdrawal Syndrome / psychology*
  • Tobacco Use Disorder / psychology*


  • Nicotinic Agonists
  • Nicotine