Exploring the effects of adolescent social isolation stress on the serotonin system and ethanol-motivated behaviors.

IF 3.3 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-04 DOI:10.1007/s00213-025-06749-3

Bryan D McElroy, Chen Li, Nicholas S McCloskey, Amber R Alberici, Lynn G Kirby

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Abstract

Rationale: Alcohol is one of the most frequently used drugs of abuse and has a major impact on human health worldwide. People assigned female at birth and those with adverse childhood experiences are stress-vulnerable and more likely to report drinking as a means of "self-medication." Prior studies in our laboratory showed that adolescent social isolation stress (SIS) increases vulnerability to ethanol (EtOH) intake and consumption despite negative consequences in female rats.

Objectives: Here, we explored modulation of the dorsal raphe nucleus (DRN)-serotonin (5-HT) system, a sexually dimorphic neurotransmitter system involved in stress-reward interactions, to determine its contribution to EtOH-motivated behaviors in rats that have undergone SIS.

Results: We employed electrophysiological and functional neuroanatomy strategies to show that both SIS and EtOH exposure induce persistent hypofunction of the DRN 5-HT system, particularly in females. Chemogenetic activation of DRN 5-HT neurons attenuated reward value for both EtOH and sucrose and elevated punished responding for EtOH in a stress-dependent manner.

Conclusions: Our results highlight an inverse relationship between EtOH consumption and the 5-HT system, the sex- and stress-dependent nature of this relationship, and a connection between DRN 5-HT signaling and acute responding to rewards and punishment. These data support the DRN 5-HT system as a potential target to treat aberrant alcohol consumption and drinking despite negative consequences in stress-vulnerable populations.

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探讨青少年社会孤立压力对血清素系统和酒精动机行为的影响。

理由：酒精是最常被滥用的药物之一，对全世界的人类健康有重大影响。出生时被指定为女性的人，以及那些有不良童年经历的人，更容易受到压力的影响，更有可能将饮酒作为一种“自我治疗”的手段。我们实验室先前的研究表明，青春期社会隔离压力（SIS）增加了雌性大鼠对乙醇（EtOH）摄入和消耗的脆弱性，尽管有负面影响。目的：在这里，我们探讨了中隔背核(DRN)- 5-羟色胺（5-HT）系统的调节，这是一种涉及应激-奖励相互作用的两性二态神经递质系统，以确定其在经历SIS的大鼠中对etoh动机行为的贡献。结果：我们采用电生理学和功能神经解剖学策略表明，暴露于SIS和EtOH都会导致DRN 5-HT系统的持续功能低下，尤其是在女性中。DRN - 5-HT神经元的化学激活以应激依赖的方式降低了EtOH和蔗糖的奖励值，并提高了对EtOH的惩罚反应。结论：我们的研究结果强调了EtOH消耗与5-羟色胺系统之间的反比关系，这种关系的性别和压力依赖性，以及DRN 5-羟色胺信号传导与奖励和惩罚的急性反应之间的联系。这些数据支持DRN 5-HT系统作为治疗异常饮酒和饮酒的潜在靶点，尽管对压力易感人群有负面影响。

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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.