Operant self-administration of alcohol and nicotine in a preclinical model of co-abuse.

PMID 24696081


Alcohol and nicotine are often taken together. In humans, intake of nicotine, via smoked tobacco, increases alcohol drinking, and alcohol increases smoking. Chronic nicotine treatment increases alcohol self-administration (SA) in laboratory animals; the reverse relationship is less clear. Most animal work modeling this has used passive administration, which lacks relevance to human co-abuse. Here, we describe a model based on sequential operant SA of alcohol and nicotine. Animals are first trained on alcohol SA (0.19 ml of 12 % alcohol (w/v)/delivery) and then receive separate alcohol (8 %, w/v) and nicotine (15 μg/kg/infusion) SA sessions on the same day ("daily dual access"). Animals then receive access to alcohol and then to nicotine (or in the reverse order) in alternating 5-min periods in 2-h sessions ("alternating access"). We then determine if alternating access modifies the effects of naltrexone on responding for alcohol and nicotine. We found that with daily dual access, nicotine significantly increased alcohol SA when alcohol access occurred prior to nicotine access and that nicotine SA significantly decreased when the alcohol SA session preceded it. During alternating access, nicotine also significantly increased alcohol intake. Naltrexone (0.3 or 1 mg/kg) significantly reduced alcohol SA during these alternating access sessions in animals that also received nicotine SA, but had minimal effects on animals receiving alcohol SA alone. Naltrexone did not affect nicotine SA under any condition. This sequential access procedure effectively models the effects of nicotine on alcohol intake noted in humans.