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Astrocyte Regulation of Stress- and Ethanol Dependence-Induced Changes in Reward Seeking
Abstract   Open access

Astrocyte Regulation of Stress- and Ethanol Dependence-Induced Changes in Reward Seeking

Laura L. Giacometti, Kelsey Chandran and Jacqueline M. Barker
Alcohol (Fayetteville, N.Y.), v 109, pp 67-67
Jun 2023
DOI: https://doi.org/10.1016/j.alcohol.2023.03.008
url
https://doi.org/10.1016/j.alcohol.2023.03.008View
Published, Version of Record (VoR)CC BY-NC-ND V4.0,  Open

Abstract

Stress-induced alterations in reward seeking are common in alcohol dependence, but this is poorly characterized in females. In preclinical models, dependent females appear to be more sensitive to aversive experience and stress-associated dysregulation of behavior. This is likely mediated in part by alterations in nucleus accumbens glutamate signaling. Astrocytes are key players in maintaining glutamate homeostasis and are sensitive to both stress and alcohol exposure in a brain region-specific manner. Here, we show that alcohol dependent females exhibit increased stress-facilitation of reward seeking and reduced nucleus accumbens astrocyte immunoreactivity when compared to nondependent females, while these patterns are not present in males. We further observe sex specific changes in astrocyte calcium signaling during reward seeking in a previously learned task, but not during extinction learning. Using a chemogenetic strategy, we show that activation of nucleus accumbens astrocytes transiently attenuates the expression of reward seeking, without promoting extinction learning in alcohol-dependent females. Unexpectedly, stress-facilitation of reward seeking was not attenuated by activation of nucleus accumbens astrocytes. This suggests that while basal reward seeking is sensitive to disruption by astrocyte activation, this is not sufficient to overcome stress-potentiated behavior. Ongoing work is characterizing the role of astrocyte function in alcohol versus food rewards. We expect that our findings will implicate astrocytes as a potential pharmacotherapeutic target for regulation of reward seeking in alcohol dependence and will advance our understanding of sex differences in the effects of alcohol dependence and neurobiology.

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Web of Science research areas
Pharmacology & Pharmacy
Substance Abuse
Toxicology
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