Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens

Ruixiang Wang; Kanza M. Khan; Nagalakshmi Balasubramanian; Thomas James; Selvakumar Govindhasamy Pushpavathi; David Kim; Samantha Pierson; Qi Wu; Mark J. Niciu; Marco M. Hefti; Catherine A. Marcinkiewcz

doi:10.1101/2023.05.29.542761

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Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens

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Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens

Ruixiang Wang, Kanza M. Khan, Nagalakshmi Balasubramanian, Thomas James, Selvakumar Govindhasamy Pushpavathi, David Kim, Samantha Pierson, Qi Wu, Mark J. Niciu, Marco M. Hefti, …

bioRxiv

Cold Spring Harbor Laboratory

05/30/2023

DOI: 10.1101/2023.05.29.542761

PMCID: PMC10312479

PMID: 37398335

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https://doi.org/10.1101/2023.05.29.542761View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Social interaction is a core component of motivational behavior that is perturbed across multiple neuropsychiatric disorders, including alcohol use disorder (AUD). Positive social bonds are neuroprotective and enhance recovery from stress, so reduced social interaction in AUD may delay recovery and lead to alcohol relapse. We report that chronic intermittent ethanol (CIE) induces social avoidance in a sex-dependent manner and is associated with hyperactivity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN). While 5-HT DRN neurons are generally thought to enhance social behavior, recent evidence suggests that specific 5-HT pathways can be aversive. Using chemogenetic iDISCO, the nucleus accumbens (NAcc) was identified as one of 5 regions that were activated by 5-HT DRN stimulation. We then employed an array of molecular genetic tools in transgenic mice to show that 5-HT DRN inputs to NAcc dynorphin neurons drive social avoidance in male mice after CIE by activating 5-HT 2C receptors. NAcc dynorphin neurons also inhibit dopamine release during social interaction, reducing the motivational drive to engage with social partners. This study reveals that excessive serotonergic drive after chronic alcohol can promote social aversion by inhibiting accumbal dopamine release. Drugs that boost brain serotonin levels may be contraindicated for individuals with AUD.

Details

Title: Subtitle: Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
Creators: Ruixiang Wang - University of Iowa
Kanza M. Khan - Daemen College
Nagalakshmi Balasubramanian - University of Iowa
Thomas James - University of Iowa
Selvakumar Govindhasamy Pushpavathi - University of Iowa
David Kim - University of Iowa
Samantha Pierson - University of Iowa
Qi Wu - Baylor College of Medicine
Mark J. Niciu - University of Iowa
Marco M. Hefti - University of Iowa
Catherine A. Marcinkiewcz - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.05.29.542761
PMID: 37398335
PMCID: PMC10312479
Language: English
Date posted: 05/30/2023
Academic Unit: Pathology; Psychiatry; Neuroscience and Pharmacology; Iowa Neuroscience Institute
Record Identifier: 9984441704602771

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