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

Sci Rep. 2017 May 30;7(1):2479. doi: 10.1038/s41598-017-02177-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alcohol Drinking / epidemiology
  • Alcohol Drinking / genetics
  • Alcohol Drinking / physiopathology*
  • Alcohols / administration & dosage
  • Alcohols / adverse effects*
  • Animals
  • Conditioning, Operant
  • Gene Expression Regulation / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Humans
  • Male
  • Nicotine / administration & dosage
  • Nicotine / adverse effects*
  • Rats
  • Self Administration
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / genetics
  • Substance-Related Disorders / physiopathology*

Substances

  • Alcohols
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nicotine