Interactive effects of ethanol and nicotine on learning, anxiety, and locomotion in C57BL/6 mice in the plus-maze discriminative avoidance task

Introduction: Alcohol and nicotine both alter learning, locomotion, and anxiety, yet no study has directly examined the interactive effects of these drugs across these behaviors within subjects. Such a comparison would determine if the drugs produce independent effects on each behavior. The plus-maze discriminative avoidance task (PMDAT) allows within-subject measurement of these behaviors. Methods: For training, each mouse explored the elevated plus-maze for 5 min and each time a mouse entered the aversive enclosed arm, a light and white noise were turned on. For testing, each mouse was returned to the center of the maze and, for 3 min, the time in each arm or in the center area was recorded. No cues were turned on during testing. The effects of ethanol (0.6-2.6 g/kg 15 min before training) and nicotine (0.045-0.18 mg/kg 5 min before training), alone or in combination, on behavior were examined. Results: Ethanol dose-dependently decreased anxiety, increased locomotion, and decreased learning but different doses altered each behavior. Nicotine dose-dependently increased anxiety and locomotion and decreased learning but different doses altered each behavior. Nicotine (0.09 mg/kg) reversed ethanol-associated changes in learning (1.0 and 1.4 g/kg), locomotion (1.4 g/kg), and anxiety (1.4 g/kg). Conclusions: The effects of nicotine or ethanol on learning occurred at different doses than those that altered anxiety or locomotion, suggesting that the drug effects on learning are independent of the effects on anxiety and locomotion. With combined administration, nicotine reduced ethanol-associated deficits in learning and changes in anxiety and locomotion.