Effects of stress, acute alcohol treatment, or both on pre-pulse inhibition in high- and low-alcohol preferring mice

Pre-pulse inhibition of the acoustic startle reflex (PPI) is a measure of sensorimotor gating frequently used to assess information processing in both humans and rodents. Both alcohol and stress exposure can modulate PPI, making it possible to assess how stress and alcohol interact to influence information processing. Humans with an increased genetic risk for alcoholism are more reactive to stressful situations compared to those without a family history, and alcohol may have stress-dampening effects for those with high genetic risk. The purpose of the present study was to examine the effects of stress, acute alcohol exposure, or both on PPI in male and female mice selectively bred for high- (HAP2) and low- (LAP2) alcohol preference. Experiment 1 assessed the effects of various doses of acute alcohol on PPI. Experiments 2 and 3 assessed the effect of 10 days of restraint stress on subsequent PPI tested at 30 min (Experiment 2) or 24 h (Experiment 3) following the termination of stress exposure. Experiment 3 also examined the effects of acute alcohol treatment (0.75 g/kg) on PPI in mice previously exposed to stress or no stress. Results indicate that 0.75 and 1.0 g/kg doses of alcohol increased PPI in HAP2 but not LAP2 mice. When PPI was tested 30 min after stress exposure, stressed HAP2 mice showed a trend toward decreased PPI and stressed LAP2 mice showed a trend toward increased PPI. The combination of stress and alcohol treatment did not alter PPI in either line 24 h following the termination of stress exposure, suggesting that alcohol does not ameliorate the effect of stress on PPI. Stressed LAP2 mice had increased basal circulating corticosterone on the final stress exposure day compared to non-stressed LAP2 mice, and no difference was found between stressed and non-stressed HAP2 mice. The results suggest that high genetic risk for alcoholism may be related to increased sensitivity to alcohol and stress effects on PPI, and this sensitivity could signify an endophenotype for increased genetic risk to develop alcoholism