Corticosterone after early adolescent stress prevents social avoidance, aversive behavior, and morphine-conditioned place preference in adulthood.

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-10-01 Epub Date: 2024-05-28 DOI:10.1007/s00213-024-06616-7

Samantha O Vanderhoof, Carly J Vincent, Jasmin N Beaver, Maeson S Latsko, Ricardo Aguilar-Alvarez, Aaron M Jasnow

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Abstract

Rationale: 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.

Objectives: 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.

Methods and results: 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.

Conclusions: 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.

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青春期早期应激后的皮质酮可预防成年后的社交回避、厌恶行为和吗啡条件性场所偏好。

理由：童年或青少年时期的压力会增加成年后患精神疾病的几率。在成年啮齿动物中，应激的延迟效应会增加焦虑样行为。然而，在应激后施用皮质酮（CORT）可以防止这些影响。CORT在预防青少年应激引起的成年期情绪行为改变方面的有效性还有待研究：在此，我们研究了早期青春期应激和外源性皮质酮对小鼠成年后社交、厌恶和觅药行为的交互作用，这些行为与精神疾病和药物滥用障碍的相关症状有转化关系：在社交失败或情境恐惧条件反射后的24小时内，在饮用水中一次性给予CORT（400ug/mL），可防止失败诱发的社交回避，改变恐惧处理，防止青春期应激诱发的失乐症，并防止成年期应激促进的吗啡位置偏好。外源性促肾上腺皮质激素并不能立即防止青少年小鼠因压力而产生的吗啡条件性位置偏好强化，但却能防止成年小鼠产生吗啡条件性位置偏好强化。然而，当对青少年小鼠施用 CORT 时，它还能防止吗啡条件性位置偏好潜伏到成年期。最后，外源性 CORT 会减弱内源性皮质酮，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皮质酮促进社会情感恢复力并防止寻求毒品行为。我们的数据表明，应激后皮质酮的升高能促进从青春期到成年期至少 40 天的恢复能力，并对社会情感和觅药行为有效。这些结果对于了解青春期压力如何影响成年后的情绪和觅药行为至关重要。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.