University of California San Diego, La Jolla, CA, USA.
Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland, Australia.
Psychopharmacology (Berl). 2018 Mar;235(3):737-747. doi: 10.1007/s00213-017-4789-0. Epub 2017 Nov 27.
Adolescent alcohol exposure may increase depression vulnerability in adulthood by increasing the anhedonic response to stress.
Male Wistar rats (postnatal days 28-53) were exposed to binge-like adolescent intermittent ethanol (AIE) or water. In adulthood, rats were exposed to social defeat, consisting of daily confrontations with an aggressive conspecific, followed by testing of brain reward function in a discrete-trial current-intensity intracranial self-stimulation procedure for 10 consecutive days. Neurochemistry and corticotropin-releasing factor (CRF) and CRF receptor 1 (CRFR1) mRNA levels were assessed in corticolimbic brain areas on day 11 of social defeat stress.
Social defeat elevated reward thresholds in both AIE- and water-exposed rats indicating stress-induced anhedonia. However, AIE-exposed rats were more likely to show threshold elevations after repeated stress compared to water-exposed rats. AIE exposure decreased CRF mRNA levels in the nucleus accumbens and increased CRFR1 mRNA levels in the prefrontal cortex, while stress increased CRF mRNA levels in the central amygdala. In the caudate putamen, AIE exposure decreased dopamine turnover, while stress increased glutamate and serotonin metabolism and turnover.
These results demonstrate increased risk of repeated stress-induced anhedonia after AIE exposure, an effect that may be due to alterations in brain CRF and dopamine systems. These results suggest that the increased rates of depression reported in people with a history of adolescent alcohol exposure may be related to alterations in brain reward and stress systems that may contribute to increased stress-induced anhedonia.
青少年期酒精暴露可能会增加对压力的快感缺失反应，从而增加成年后抑郁的易感性。
雄性 Wistar 大鼠（出生后第 28-53 天）接受 binge-like 青少年间歇性乙醇（AIE）或水暴露。成年后，大鼠接受社交挫败，包括每天与一个攻击性同种动物对抗，然后在连续 10 天的离散试验电流强度颅内自我刺激程序中测试大脑奖励功能。在社交挫败应激的第 11 天，评估皮质边缘脑区的神经化学物质和促肾上腺皮质释放因子（CRF）和 CRF 受体 1（CRFR1）mRNA 水平。
社交挫败提高了 AIE 和水暴露的大鼠的奖励阈值，表明应激引起的快感缺失。然而，与水暴露的大鼠相比，AIE 暴露的大鼠在反复应激后更有可能出现阈值升高。AIE 暴露降低了伏隔核中的 CRF mRNA 水平，增加了前额叶皮层中的 CRFR1 mRNA 水平，而应激增加了杏仁中央核中的 CRF mRNA 水平。在尾壳核中，AIE 暴露降低了多巴胺的周转率，而应激增加了谷氨酸和血清素的代谢和周转率。
这些结果表明，AIE 暴露后，反复应激引起的快感缺失的风险增加，这种效应可能是由于大脑 CRF 和多巴胺系统的改变。这些结果表明，有青少年期酒精暴露史的人报告的抑郁发生率增加可能与大脑奖励和应激系统的改变有关，这些改变可能导致应激引起的快感缺失增加。
