A common genetic predisposition to stress sensitivity and stress-induced nicotine craving

Biol Psychiatry. 2008 Jan 15;63(2):164-71. doi: 10.1016/j.biopsych.2007.02.010. Epub 2007 Jun 13.

Abstract

Background: Clinical studies have shown that stress is one of the main causes for relapse in abstinent smokers. In this article, we have asked whether animals with a genetic predisposition to high or low stress responsivity differ in behaviors relevant to nicotine addiction, in particular stress-induced reinstatement of drug addiction.

Methods: First, we selected animals with high, low, and average stress sensitivity from the F2 generation from an intercross of high (C57BL/6J) and low (C3H/J) emotional mouse strains. Next, these animals were trained to self-administer nicotine through a chronic intravenous catheter. After extinction of the operant behavior replacing nicotine with saline, mice were stressed with a foot shock and the reinstatement of drug-seeking behaviors was evaluated.

Results: Mice with different stress reactivity showed no difference in the acquisition, extinction, or level of nicotine self-administration. We found an immediate reinstatement of drug-seeking behavior in high stress reactive mice, in contrast to low or average stress reactive animals, which showed no significantly increased activity at the active (nicotine-associated) sensor.

Conclusions: We conclude that a genetic predisposition to high stress sensitivity contributes to relapse vulnerability but not to the initiation or maintenance of nicotine consumption.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Genetic Predisposition to Disease*
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nicotine / administration & dosage
  • Principal Component Analysis
  • Reflex, Startle / physiology
  • Reflex, Startle / radiation effects
  • Reinforcement, Psychology
  • Self Administration
  • Stress, Psychological / complications*
  • Stress, Psychological / genetics*
  • Swimming
  • Tobacco Use Disorder / etiology*
  • Tobacco Use Disorder / genetics
  • Tobacco Use Disorder / psychology*

Substances

  • Nicotine