A Common Genetic Predisposition to Stress Sensitivity and Stress-Induced Nicotine Craving

Abstract

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