Bonauto S M, Brunke O R, Vassoler F M, Weera M M
Department of Psychology, Tufts University, Medford, MA, USA; Neuroscience Program, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, USA.
Department of Psychology, Tufts University, Medford, MA, USA.
Neuropharmacology. 2025 Sep 15;276:110511. doi: 10.1016/j.neuropharm.2025.110511. Epub 2025 May 13.
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.
创伤性应激会导致一些人出现适应不良的回避行为和酒精滥用。在大鼠中，捕食者气味（“创伤性”）应激会使一些动物（回避者）持续回避与应激相关的环境，并增加酒精的自我给药量，而另一些动物（非回避者）则不会，这反映了人类在应激反应性和酒精滥用方面的个体差异。在此，我们测量了雄性和雌性回避者、非回避者以及未受应激的对照组在应激后的自由选择和抗厌恶酒精饮用情况、焦虑相关行为以及下丘脑外侧区Crh、Crhr1、Crhr2和Crhbp基因的表达。应激后，雄性回避者大鼠的自由选择酒精摄入量增加，而雌性则没有，且回避程度越高，抗厌恶酒精饮用越多。使用超声波发声（USV）作为情感指标，我们发现非回避者雄性在捕食者气味应激之前、期间和之后发出的低频USV（<32 kHz）更多。最后，对下丘脑外侧区Crh、Crhr1、Crhr2和Crhbp基因表达的定量分析显示，雄性回避者大鼠的Crh表达高于非回避者和对照组，且下丘脑外侧区Crh表达越高，回避行为和酒精饮用越多。在雌性中，下丘脑外侧区Crh、Crhr1、Crhr2和Crhbp的表达越高，则预示着焦虑样行为越少。总体而言，这些结果表明，应激、酒精饮用、焦虑样行为与下丘脑外侧区CRH系统之间的关系具有性别和亚群体特异性。
