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Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens

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...

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Autores principales: Marcinkiewcz, Catherine, Wang, Ruixiang, Khan, Kanza, Balasubramanian, Nagalakshmi, James, Thomas, Pushpavathi, Selvakumar, Kim, David, Pierson, Samantha, Wu, Qi, Niciu, Mark, Hefti, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350230/
https://www.ncbi.nlm.nih.gov/pubmed/37461716
http://dx.doi.org/10.21203/rs.3.rs-2992781/v1
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author Marcinkiewcz, Catherine
Wang, Ruixiang
Khan, Kanza
Balasubramanian, Nagalakshmi
James, Thomas
Pushpavathi, Selvakumar
Kim, David
Pierson, Samantha
Wu, Qi
Niciu, Mark
Hefti, Marco
author_facet Marcinkiewcz, Catherine
Wang, Ruixiang
Khan, Kanza
Balasubramanian, Nagalakshmi
James, Thomas
Pushpavathi, Selvakumar
Kim, David
Pierson, Samantha
Wu, Qi
Niciu, Mark
Hefti, Marco
author_sort Marcinkiewcz, Catherine
collection PubMed
description 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.
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spelling pubmed-103502302023-07-17 Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens Marcinkiewcz, Catherine Wang, Ruixiang Khan, Kanza Balasubramanian, Nagalakshmi James, Thomas Pushpavathi, Selvakumar Kim, David Pierson, Samantha Wu, Qi Niciu, Mark Hefti, Marco Res Sq Article 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. American Journal Experts 2023-07-05 /pmc/articles/PMC10350230/ /pubmed/37461716 http://dx.doi.org/10.21203/rs.3.rs-2992781/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Marcinkiewcz, Catherine
Wang, Ruixiang
Khan, Kanza
Balasubramanian, Nagalakshmi
James, Thomas
Pushpavathi, Selvakumar
Kim, David
Pierson, Samantha
Wu, Qi
Niciu, Mark
Hefti, Marco
Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title_full Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title_fullStr Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title_full_unstemmed Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title_short Alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
title_sort alcohol inhibits sociability via serotonin inputs to the nucleus accumbens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10350230/
https://www.ncbi.nlm.nih.gov/pubmed/37461716
http://dx.doi.org/10.21203/rs.3.rs-2992781/v1
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