Genetic correlation between alcohol preference and conditioned fear: Exploring a functional relationship

Abstract

Post-traumatic stress disorder (PTSD) and alcohol-use disorders have a high rate of co-occurrence, possibly because they are regulated by common genes. In support of this idea, mice selectively bred for high (HAP) alcohol preference show greater fear potentiated startle (FPS), a model for fear-related disorders such as PTSD, compared to mice selectively bred for low (LAP) alcohol preference. This positive genetic correlation between alcohol preference and FPS behavior suggests that the two traits may be functionally related. This study examined the effects of fear conditioning on alcohol consumption and the effects of alcohol consumption on the expression of FPS in male and female HAP2 and LAP2 mice. In experiment 1, alcohol consumption (g/kg) under continuous-access conditions was monitored daily for 4 weeks following a single fear-conditioning or control treatment (foot shock and no shock). FPS was assessed three times (once at the end of the 4-week alcohol access period, once at 24 h after removal of alcohol, and once at 6–8 days after removal of alcohol), followed by two more weeks of alcohol access. Results showed no change in alcohol consumption, but alcohol-consuming, fear-conditioned, HAP2 males showed increased FPS at 24 h during the alcohol abstinence period compared to control groups. In experiment 2, alcohol consumption under limited-access conditions was monitored daily for 4 weeks. Fear-conditioning or control treatments occurred four times during the first 12 days and FPS testing occurred four times during the second 12 days of the 4-week alcohol consumption period. Results showed that fear conditioning increased alcohol intake in both HAP2 and LAP2 mice immediately following the first conditioning session. Fear-conditioned HAP2 but not LAP2 mice showed greater alcohol intake compared to control groups on drinking days that occurred between fear conditioning and FPS test sessions. FPS did not change as a function of alcohol consumption in either line. These results in mice help shed light on how a genetic propensity toward high alcohol consumption may be related to the risk for developing PTSD and co-morbid alcohol-use disorders in humans.

BNST specific mGlu5 receptor knockdown regulates sex-dependent expression of negative affect produced by adolescent ethanol exposure and adult stress

“…Previous work has indicated that high alcohol-preferring mice exposed to cued fear conditioning and allowed free access to alcohol show enhanced hypervigilance in the fear-potentiated startle task, regardless of sex. However, fear conditioning only caused immediate increases in alcohol intake in male mice 58 . Another model using unpredictable chronic mild stress showed that an alcohol history plus stress increased binge drinking in male, but not female, mice 59 .…”

Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference

“…Female rats show greater motivation to self-administer nicotine than male rats (Donny et al, 2000). Additionally, the heritability of smoking has been shown to be higher in women than in men (Pogun et al, 2017) and alcohol intake is higher in female HAP2 and LAP2 mice than in males (Chester and Weera, 2017; Oberlin et al, 2010); thus, the use of females might improve the detection of nicotine-alcohol interactive effects in HAP2 and LAP2 mice.…”