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

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub 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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引用次数: 0

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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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.