Effects of Ethanol and Caffeine on Behavior in C57BL/6 Mice in the Plus-Maze Discriminative Avoidance Task

Introduction: Caffeine is frequently consumed concurrent to or immediately following ethanol consumption. Identifying how caffeine and ethanol interact to modulate behavior is essential to understanding the co-use of these drugs. The plus-maze discriminative avoidance task (PMDAT) allows within-subject measurement of learning, anxiety, and locomotion. Methods: For training, each mouse was placed in the center of the plus-maze for 5 min, and each time that the mouse entered the aversive enclosed arm, a light and white noise were turned on. At testing, each mouse was returned to the center of the maze for 3 min. No cues were turned on during testing. Results: Ethanol (1.0-1.4 g/kg) dose-dependently decreased anxiety and learning, and increased locomotion. Caffeine (5.0-40.0 mg/kg) dose-dependently increased anxiety and decreased locomotion and learning. Caffeine failed to reverse ethanol-induced learning deficits. However, 1.4 g/kg ethanol blocked the anxiogenic effect of caffeine. Discussion: Although caffeine and ethanol interact to modulate behavior in the PMDAT, caffeine does not reverse ethanol-induced learning deficits. Ethanol-induced anxiolysis may contribute to alcohol consumption, while ethanol's blockade of caffeine-induced anxiogenesis may contribute to co-use.