Original Investigation


, Volume 196, Issue 3, pp 483-495

First online:

Interactive effects of ethanol and nicotine on learning in C57BL/6J mice depend on both dose and duration of treatment

  • Danielle GulickAffiliated withDepartment of Psychology, Neuroscience Program, Temple University
  • , Thomas J. GouldAffiliated withDepartment of Psychology, Neuroscience Program, Temple UniversityDepartment of Psychology, Center for Substance Abuse Research, Temple University Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


Objective and rationale

Alcohol and nicotine are commonly co-abused; one possible explanation for co-abuse is that each drug ameliorates the aversive effects of the other. Both drugs have dose-dependent effects on learning and memory. Thus, this study examined the interactive effects of acute ethanol and acute, chronic, or withdrawal from chronic nicotine on fear conditioning in C57BL/6J mice.

Materials and methods

Conditioning consisted of auditory conditioned stimulus-foot-shock unconditioned stimulus pairings. For acute studies, saline or ethanol, then saline or nicotine was administered before training, and saline or nicotine was also administered before testing. For chronic and withdrawal studies, saline or nicotine was administered chronically, and ethanol or saline was administered before training.


Acute nicotine (0.09 mg/kg) reversed ethanol-induced deficits (1.0 and 1.5 g/kg) in contextual and cued fear conditioning, whereas a low dose of ethanol (0.25 g/kg) reversed nicotine (6.3 mg kg−1 day−1) withdrawal-induced deficits in contextual conditioning. Tolerance developed for the effects of nicotine on ethanol-induced deficits in conditioning and cross-tolerance between chronic nicotine and acute ethanol was seen for the enhancing effects of ethanol on conditioning.


The complex and sometimes polar actions of ethanol and nicotine on behavior may contribute to co-abuse of these drugs. Specifically, smoking may initially reduce the aversive effects of ethanol, but tolerance develops for this effect. In addition, low doses of alcohol may lessen nicotine withdrawal symptoms.


Addiction Learning Withdrawal Tolerance Acetylcholine