Department of Psychological Sciences, Brain Health Research Institute, Kent State University, Kent, USA.
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, USA.
Psychopharmacology (Berl). 2024 Oct;241(10):2045-2059. doi: 10.1007/s00213-024-06616-7. Epub 2024 May 28.
Stress during childhood or adolescence increases vulnerability to psychiatric disorders in adults. In adult rodents, the delayed effects of stress can increase anxiety-like behavior. These effects, however, can be prevented with post-stress administration of corticosterone (CORT). The effectiveness of CORT in preventing adolescent stress-induced emotional behavior alterations in adulthood has yet to be investigated.
Here, we investigated the interactions between early adolescent stress and exogenous corticosterone on adult social, aversive, and drug-seeking behavior in mice, which are translationally related to symptoms associated with psychiatric and substance abuse disorders.
A single administration of CORT in drinking water (400ug/mL) for 24 h after social defeat or context fear conditioning prevents defeat-induced social avoidance, alters fear processing, prevents adolescent stress-induced anhedonia, and prevents stress-potentiated morphine place preference in adulthood. Exogenous CORT did not immediately prevent stress-induced potentiation of morphine conditioned-place preference in adolescents but did so in adult mice. However, when administered to adolescent mice, CORT also prevented the incubation of morphine-conditioned place preference into adulthood. Lastly, exogenous CORT administration blunted endogenous corticosterone but was unrelated to freezing behavior during a fear test.
This is the first demonstration of adolescent post-stress CORT promoting socio-emotional resilience and preventing drug-seeking behavior. Our data suggest elevated corticosterone after a stress experience promotes resilience for at least 40 days across the developmental transition from adolescence to adulthood and is effective for socio-emotional and drug-seeking behavior. These results are critical for understanding how adolescent stress impacts emotional and drug-seeking behavior into adulthood.
儿童或青少年时期的压力会增加成年后患精神疾病的易感性。在成年啮齿动物中，压力的延迟效应会增加类似焦虑的行为。然而，这些效应可以通过应激后给予皮质酮（CORT）来预防。皮质酮在预防成年期青少年应激引起的情绪行为改变方面的有效性尚未得到研究。
本研究旨在探讨早期青少年应激和外源性皮质酮对成年社交、厌恶和觅药行为的相互作用，这些行为与精神疾病和物质滥用障碍相关症状有关。
社交挫败或情境恐惧条件作用后，在饮用水中单次给予皮质酮（400μg/ml）24 小时，可以预防挫败引起的社交回避，改变恐惧处理，预防青少年应激引起的快感缺失，并预防应激增强成年期吗啡位置偏好。外源性 CORT 不能立即预防应激增强青少年吗啡条件性位置偏好，但可以预防成年期小鼠的应激增强吗啡条件性位置偏好。然而，当给予青少年小鼠时，CORT 也预防了吗啡条件性位置偏好向成年期的潜伏期。最后，外源性 CORT 给药减弱了内源性皮质酮，但与恐惧测试中的冻结行为无关。
这是首次证明青少年应激后 CORT 促进社会情感弹性并预防觅药行为。我们的数据表明，应激后升高的皮质酮至少在从青少年到成年的发育过渡期间促进了 40 天的弹性，并且对社会情感和觅药行为有效。这些结果对于理解青少年应激如何影响成年期的情绪和觅药行为至关重要。
