Original Investigation


, Volume 168, Issue 1, pp 216-221

First online:

Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats

  • A. D. LêAffiliated withCentre for Addiction and Mental HealthDepartment of Pharmacology, University of TorontoDepartment of Psychiatry, University of Toronto Email author 
  • , A. WangAffiliated withDepartment of Pharmacology, University of Toronto
  • , S. HardingAffiliated withCentre for Addiction and Mental Health
  • , W. JuzytschAffiliated withCentre for Addiction and Mental Health
  • , Y. ShahamAffiliated withBehavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS

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Rationale and objective

Alcohol and tobacco are often co-abused in humans and previous studies found that nicotine increases alcohol consumption in rats. Here, we studied whether nicotine would reinstate alcohol-taking behavior in drug-free rats and whether this effect would be enhanced by prior exposure to nicotine during alcohol self-administration training.


Rats were trained to press a lever for alcohol (12% w/v, 1 h/day), and following stable alcohol intake groups of rats (n=11–12) were given daily vehicle or nicotine (0.2, 0.4 or 0.8 mg/kg, SC) injections just prior to the self-administration sessions for 10 days. Rats were then given 6 days of alcohol self-administration in the absence of nicotine and an additional 5–10 drug-free days during which lever presses were not reinforced (extinction). Subsequently, rats were tested for reinstatement of alcohol seeking following exposure to priming injections of vehicle or nicotine (0.4 mg/kg, SC).


Nicotine increased alcohol self-administration in a dose- and time-dependent manner over the 10-day period. Nicotine also reinstated alcohol seeking after extinction of the alcohol-reinforced behavior, and this effect was strongly enhanced by prior nicotine exposure.


The present data extend previous studies on the effect of nicotine on alcohol self-administration, and further indicate that nicotine is an effective stimulus for reinstatement of alcohol seeking during drug-free periods.


Alcohol Extinction Nicotine Reinstatement Relapse Self-administration