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Sex-specific regulation of binge drinking and affective behaviors by subcortical serotonin 5HT2c receptors

View ORCID ProfileM.E. Flanigan, O.J. Hon, S. D’Ambrosio, K.M. Boyt, L. Hassanein, M. Castle, H.L. Haun, M.M. Pina, T.L. Kash
doi: https://doi.org/10.1101/2022.01.28.478036
M.E. Flanigan
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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  • ORCID record for M.E. Flanigan
O.J. Hon
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
3Curriculum in Neuroscience, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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S. D’Ambrosio
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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K.M. Boyt
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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L. Hassanein
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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M. Castle
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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H.L. Haun
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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M.M. Pina
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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T.L. Kash
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA
2Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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  • For correspondence: thomas_kash@med.unc.edu
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Summary

Serotonin 5HT2c receptors have been implicated in the pathophysiology of both mood disorders and substance use disorders, but the precise cells and circuits mediating the effects on behavior have yet to be identified. In this study, we employed anatomical tracing, in-vivo fiber photometry with both calcium and serotonin sensors, electrophysiology, chemogenetics, and genetic manipulations of the 5HT2c receptor to identify two populations of neurons expressing serotonin 5HT2c receptors, one in the lateral habenula and one in the bed nucleus of the stria terminalis, that sex-specifically co-regulate affective behaviors and are modulated by binge alcohol consumption. These findings may have implications for the development of sex-specific treatments for mood disorders and substance use disorders targeting the brain’s serotonin system.

Competing Interest Statement

The authors have declared no competing interest.

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Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 28, 2022.
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Sex-specific regulation of binge drinking and affective behaviors by subcortical serotonin 5HT2c receptors
M.E. Flanigan, O.J. Hon, S. D’Ambrosio, K.M. Boyt, L. Hassanein, M. Castle, H.L. Haun, M.M. Pina, T.L. Kash
bioRxiv 2022.01.28.478036; doi: https://doi.org/10.1101/2022.01.28.478036
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Sex-specific regulation of binge drinking and affective behaviors by subcortical serotonin 5HT2c receptors
M.E. Flanigan, O.J. Hon, S. D’Ambrosio, K.M. Boyt, L. Hassanein, M. Castle, H.L. Haun, M.M. Pina, T.L. Kash
bioRxiv 2022.01.28.478036; doi: https://doi.org/10.1101/2022.01.28.478036

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