Amy E Chan, Justin Q Anderson, Kolter B Grigsby, Bryan E Jensen, Andrey E Ryabinin, Angela R Ozburn
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引用次数: 0
Abstract
Rationale: Women tend to progress from initial alcohol use to Alcohol Use Disorder (AUD) more quickly than men, highlighting the need to study sex differences in models of early-stage alcohol use. In humans and rodents, the nucleus accumbens (NAc) regulates alcohol binge drinking, a risk factor for developing AUD. However, it is unknown whether similar brain regions and NAc inputs are engaged in males and females during binge-like drinking.
Methods: We labeled NAc inputs with a viral retrograde tracer (GFP) and quantified whole-brain c-Fos to determine the regions and NAc inputs differentially engaged in male and female mice during binge-like drinking. Mice underwent a 4-day Drinking-in-the-Dark task for either ethanol or water. Immediately following drinking on day 4, periorbital blood samples were collected for determination of blood ethanol concentration, and brains were collected. c-Fos expression and c-Fos + GFP colocalization was quantified for 426 brain areas using SmartAnalytics. We employed several data and network analysis approaches to identify NAc circuits and regions engaged, and network dynamics altered by binge-like drinking.
Results: We found that ethanol engaged significantly more NAc inputs in binge-like ethanol drinking females, as compared to males, including various GABAergic and glutamatergic regions. Moreover, we found that binge-like drinking females had 129 brain areas with greater c-Fos than males. Relative to water controls, ethanol increased network modularity and decreased connectivity in both sexes and did so more dramatically in males.
Conclusion: Our results support that early-stage binge-like ethanol drinking engages brain regions and NAc inputs and alters network dynamics in a sex-specific manner, which may help to explain the faster transition from initial alcohol use to AUD in women.
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.
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