Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell

A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly in...

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Autores principales:	Sheketha R. Hauser, Patrick J. Mulholland, William A. Truitt, R. Aaron Waeiss, Eric A. Engleman, Richard L. Bell, Zachary A. Rodd
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adolescent alcohol dopamine self-administration Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/00a90f1f1abd4d29b02b013640690ede
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spelling	oai:doaj.org-article:00a90f1f1abd4d29b02b013640690ede2021-11-11T17:11:17ZAdolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell10.3390/ijms2221117331422-00671661-6596https://doaj.org/article/00a90f1f1abd4d29b02b013640690ede2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11733https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (<i>Chrna7</i>, <i>Impact</i>, <i>Chrna5</i>). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.Sheketha R. HauserPatrick J. MulhollandWilliam A. TruittR. Aaron WaeissEric A. EnglemanRichard L. BellZachary A. RoddMDPI AGarticleadolescent alcoholdopamine self-administrationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11733, p 11733 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adolescent alcohol dopamine self-administration Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	adolescent alcohol dopamine self-administration Biology (General) QH301-705.5 Chemistry QD1-999 Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
description	A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (<i>Chrna7</i>, <i>Impact</i>, <i>Chrna5</i>). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.
format	article
author	Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd
author_facet	Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd
author_sort	Sheketha R. Hauser
title	Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
title_short	Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
title_full	Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
title_fullStr	Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
title_full_unstemmed	Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
title_sort	adolescent intermittent ethanol (aie) enhances the dopaminergic response to ethanol within the mesolimbic pathway during adulthood: alterations in cholinergic/dopaminergic genes expression in the nucleus accumbens shell
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/00a90f1f1abd4d29b02b013640690ede
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Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell

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