Investigating the Effects of Juvenile Stress on Contextual Fear and Unconditioned Anxiety Related Behavior in Mice Selectively Bred for High and Low Alcohol Preference

Juvenile stress (JS) is a known risk factor for the development of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD), both of which frequently occur together, suggesting common genetic influences on vulnerability toward these disorders. The present study investigated the impact of JS on contextual fear learning and extinction, as well as corticosterone (CORT) responses before and after JS, before and after contextual fear conditioning (CFC), and after fear extinction in male and female high-alcohol-preferring (HAP2) and low-alcohol-preferring (LAP2) mice. We also measured unconditioned anxiety-related behavior in the light-dark-transition test. No line differences were seen in fear acquisition, however, HAP2 mice showed faster fear extinction compared to LAP2 mice. No effects of JS were seen in HAP2 mice, whereas in LAP2 mice, JS reduced fear acquisition in males and facilitated fear extinction in females. Females showed greater fear relative to males, regardless of subgroup. Anxiety-related behavior, assessed by the light-dark transition test, did not correspond with fear-related behavior, as LAP2 females demonstrated more anxiolytic-like responses than LAP2 males, while HAP2 males demonstrated more anxiolytic-like responses than LAP2 males. There were no line differences in CORT during the juvenile stage; however, adult LAP2 mice showed greater CORT levels than HAP2 mice at baseline and after CFC and extinction testing. These findings provide new information regarding fear learning and extinction in these unique mouse lines that model mechanisms theorized to contribute to co-morbid AUD and PTSD.