Effects of ethanol and caffeine on behavior in C57BL/6 mice in the plus-maze discriminative avoidance task

Abstract

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.

Figure 1

Effects of caffeine administered at training. (A-B) Effects on learning [percent time in the aversive and non-aversive enclosed arms]. A) Caffeine did not alter time in the aversive arm or non-aversive arm at training. B) Caffeine (40 mg/kg) increased time in the aversive arm and decreased time in the non-aversive arm at testing (n=8-10; Mean ± SEM; * = significantly different from controls and + = significant difference between arms at p<0.05). (C-D) Effects on anxiety [percent time in the open arms]: C) Caffeine dose-dependently decreased time in the open arms at training. D) There was no change in anxiety at testing (n=8-10; Mean ± SEM; * = significantly different from controls at p<0.05). (E-F) Effects on locomotion [total arm entries]: There were no significant differences between groups at training (E) or testing (F) (n=8-10; Mean ± SEM).

Figure 2

Effects of caffeine (40 mg/kg) administered at training only vs. at training and testing on learning [percent time in the aversive and non-aversive arms]. A) There were no differences between groups at training. B) Both caffeine-treated groups spent more time in the aversive arm and less time in the non-aversive arm than saline controls at testing (n = 6; Mean ± SEM; * = significantly different from controls and + = significant difference between arms at p<0.05).

Figure 3

Effects of 1.0 g/kg ethanol and caffeine (20-40 mg/kg) administered at training. (A-B) Effects on learning [percent time in the aversive and non-aversive enclosed arms]: A) Caffeine (20 and 40 mg/kg) increased time in the non-aversive arm at training, and ethanol blocked this effect. B) Both caffeine (40 mg/kg) and ethanol increased time in the aversive arm and decrease time in the non-aversive arm at testing (n=6-7; Mean ± SEM; * = significantly different from controls and + = significant difference between arms at p<0.05). (C-D) Effects on anxiety [percent time in the open arms]: C) Caffeine decreased time in the open arms at training, and ethanol reversed this effect. D) Ethanol administered at training increased time in the open arms at testing, but there were no other group effects (n=6-7; Mean ± SEM; * = significantly different from controls at p<0.05). (E-F) Effects on locomotion [total arm entries]: E) 40 mg/kg caffeine decreased locomotion at training. F) There were no differences between groups at testing (n=8-10; Mean ± SEM; * = significantly different from controls at p<0.05).

Figure 4

Effects of caffeine (40 mg/kg) and ethanol (1.4 g/kg) administered at training. (A-B) Effects on learning [percent time in the aversive and non-aversive arms]: A) Both ethanol-treated groups spent less time in the non-aversive arm than saline controls at training. B) All experimental groups spent more time in the aversive arm and less time in the non-aversive arm than saline controls at testing (n = 6; Mean ± SEM; * = significantly different from controls at p<0.05). (C-D) Effects on anxiety [percent time in the open arms]: C) Ethanol increased time in the open arms at training. D) Ethanol increased time in the open arms and caffeine blocked this effect at testing (n=8-10; Mean ± SEM; * = significantly different from controls at p<0.05). (E-F) Effects on locomotion [total arm entries]: E) Ethanol increased arm entries at training and caffeine blocked this effect. F) Ethanol increased arm entries at testing. (n=8-10; Mean ± SEM; * = significantly different from controls at p<0.05).