Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens

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

doi:10.21203/rs.3.rs-2992781/v1

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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

Catherine Marcinkiewcz, Ruixiang Wang, Kanza Khan, Nagalakshmi Balasubramanian, Thomas James, Selvakumar Pushpavathi, David Kim, Samantha Pierson, Qi Wu, Mark Niciu, …

Research Square

American Journal Experts

07/05/2023

DOI: 10.21203/rs.3.rs-2992781/v1

PMCID: PMC10350230

PMID: 37461716

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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-HTDRN 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-HT2C 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: Catherine Marcinkiewcz - University of Iowa
Ruixiang Wang - University of Iowa
Kanza Khan - Daemen College
Nagalakshmi Balasubramanian - University of Iowa
Thomas James
Selvakumar Pushpavathi - University of Iowa
David Kim - University of Iowa
Samantha Pierson - University of Iowa
Qi Wu - Baylor College of Medicine
Mark Niciu - University of Iowa
Marco Hefti - University of Iowa
Resource Type: Preprint
Publication Details: Research Square
DOI: 10.21203/rs.3.rs-2992781/v1
PMID: 37461716
PMCID: PMC10350230
Publisher: American Journal Experts
Language: English
Date posted: 07/05/2023
Academic Unit: Psychiatry; Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984445650802771

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