Predator odor stress produces sex- and subpopulation-specific increases in alcohol drinking, anxiety-like behavior, and lateral hypothalamic Crh expression

Abstract

Traumatic stress leads to maladaptive avoidance behaviors and alcohol misuse in some people. In rats, predator odor ("traumatic") stress produces persistent avoidance of stress-paired contexts and escalated alcohol self-administration in some animals (Avoiders) but not others (Non-Avoiders), mirroring the individual differences in stress responsivity and alcohol misuse seen in humans. Here, we measured post-stress free-choice and aversion-resistant alcohol drinking, anxiety-related behavior, and lateral hypothalamus Crh, Crhr1, Crhr2, and Crhbp gene expression in male and female Avoiders, Non-Avoiders, and unstressed Controls. Male but not female Avoider rats escalated their free-choice alcohol intake after stress, and greater avoidance predicted greater aversion-resistant alcohol drinking. Using ultrasonic vocalizations (USVs) as a measure of affect, we found that Non-Avoider males emitted more low frequency USVs (<32 kHz) preceding, during, and following predator odor stress. Finally, quantification of Crh, Crhr1, Crhr2, and Crhbp gene expression in the LH revealed that male Avoider rats had elevated Crh expression than Non-Avoiders and Controls, and that greater LH Crh expression correlated with more avoidance behavior and more alcohol drinking. In females, greater expression of Crh, Crhr1, Crhr2, and Crhbp in the LH all predicted less anxiety-like behavior. Collectively, these results show that the relationship between stress, alcohol drinking, anxiety-like behavior, and the LH CRH system is sex- and subpopulation-specific.

Keywords: Alcohol; Aversion; Avoidance; Crh; Lateral hypothalamus; Predator odor; Ultrasonic vocalizations.