Re-exposure to nicotine-Associated context from adolescence enhances alcohol intake in adulthood

Abstract

Alcohol and nicotine are the two most commonly-Abused substances and are often used together. Nicotine enhances alcohol-drinking behaviors in humans and in animals, and was suggested to enhance the reinforcing properties of other reinforcers. Here, we show that nicotine-Associated environment, rather than nicotine itself, enhances alcohol intake in rats. Adolescent rats received repeated intermittent injections of nicotine (0.4 mg/kg, i.p., 5 injections, every 3rd day) or saline. The injection was paired with their home cage, or with the subsequent alcohol self-Administration context. Rats were then trained to self-Administer 20% alcohol. Nicotine given in the home cage did not alter subsequent alcohol intake. However, pairing nicotine with the operant chamber during adolescence led to a long-lasting increased alcohol self-Administration in adulthood, compared to nicotine pre-Treatment in other contexts. This effect persisted 3 months after nicotine cessation, in a relapse test after abstinence. Furthermore, re-exposure to the nicotine-Associated context in adult rats led to a decrease in glial cell line-derived neurotrophic factor (Gdnf) mRNA expression in the ventral tegmental area, an effect that leads to increased alcohol consumption, as we ? have previously reported. Our findings suggest that retrieval of nicotine-Associated contextual memories from adolescence may gate alcohol intake in adulthood, with a possible involvement of GDNF.