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Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats

The nucleus accumbens (NAc), considered the hub of reward circuitry, is comprised of two medium spiny neuron (MSN) subtypes that are classified by their enrichment of dopamine 1 (D1) or 2 (D2) receptors. While reports indicate that alcohol increases excitatory neurotransmission exclusively on NAc D1...

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Autores principales: Strong, C. E., Hagarty, D. P., Brea Guerrero, A., Schoepfer, K. J., Cajuste, S. M., Kabbaj, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644642/
https://www.ncbi.nlm.nih.gov/pubmed/33154463
http://dx.doi.org/10.1038/s41598-020-76183-2
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author Strong, C. E.
Hagarty, D. P.
Brea Guerrero, A.
Schoepfer, K. J.
Cajuste, S. M.
Kabbaj, M.
author_facet Strong, C. E.
Hagarty, D. P.
Brea Guerrero, A.
Schoepfer, K. J.
Cajuste, S. M.
Kabbaj, M.
author_sort Strong, C. E.
collection PubMed
description The nucleus accumbens (NAc), considered the hub of reward circuitry, is comprised of two medium spiny neuron (MSN) subtypes that are classified by their enrichment of dopamine 1 (D1) or 2 (D2) receptors. While reports indicate that alcohol increases excitatory neurotransmission exclusively on NAc D1-MSNs in male rats, it remains unknown how NAc MSNs control alcohol intake in either sex. Therefore, this study investigated how NAc MSNs mediate alcohol intake by using Drd1a-iCre and Drd2-iCre transgenic rats of both sexes. Intra-NAc infusions of Cre-inducible viral vectors containing stimulatory (hM3Dq) or inhibitory (hM4Di) designer receptors exclusively activated by designer drugs (DREADDs) were delivered after 4-weeks of alcohol intake, and clozapine-N-oxide (CNO) was administered to selectively manipulate NAc MSNs. Our results show that activation of NAc D1-MSNs increased alcohol intake 1-, 4-, and 24-h after the start of drinking while inhibition decreased it 1-h after the start of drinking, with no sex differences observed at any time point. Activation of NAc D2-MSNs had no impact on alcohol intake while inhibition increased alcohol intake in Drd2-iCre rats for 1-h in males and 4-h in females. These findings suggest opposing roles for how NAc D1- and D2-MSNs modulate alcohol intake in rats of both sexes.
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spelling pubmed-76446422020-11-06 Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats Strong, C. E. Hagarty, D. P. Brea Guerrero, A. Schoepfer, K. J. Cajuste, S. M. Kabbaj, M. Sci Rep Article The nucleus accumbens (NAc), considered the hub of reward circuitry, is comprised of two medium spiny neuron (MSN) subtypes that are classified by their enrichment of dopamine 1 (D1) or 2 (D2) receptors. While reports indicate that alcohol increases excitatory neurotransmission exclusively on NAc D1-MSNs in male rats, it remains unknown how NAc MSNs control alcohol intake in either sex. Therefore, this study investigated how NAc MSNs mediate alcohol intake by using Drd1a-iCre and Drd2-iCre transgenic rats of both sexes. Intra-NAc infusions of Cre-inducible viral vectors containing stimulatory (hM3Dq) or inhibitory (hM4Di) designer receptors exclusively activated by designer drugs (DREADDs) were delivered after 4-weeks of alcohol intake, and clozapine-N-oxide (CNO) was administered to selectively manipulate NAc MSNs. Our results show that activation of NAc D1-MSNs increased alcohol intake 1-, 4-, and 24-h after the start of drinking while inhibition decreased it 1-h after the start of drinking, with no sex differences observed at any time point. Activation of NAc D2-MSNs had no impact on alcohol intake while inhibition increased alcohol intake in Drd2-iCre rats for 1-h in males and 4-h in females. These findings suggest opposing roles for how NAc D1- and D2-MSNs modulate alcohol intake in rats of both sexes. Nature Publishing Group UK 2020-11-05 /pmc/articles/PMC7644642/ /pubmed/33154463 http://dx.doi.org/10.1038/s41598-020-76183-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Strong, C. E.
Hagarty, D. P.
Brea Guerrero, A.
Schoepfer, K. J.
Cajuste, S. M.
Kabbaj, M.
Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title_full Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title_fullStr Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title_full_unstemmed Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title_short Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
title_sort chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644642/
https://www.ncbi.nlm.nih.gov/pubmed/33154463
http://dx.doi.org/10.1038/s41598-020-76183-2
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