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Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration

Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol...

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Autores principales: Thomas, Alyse M., Ostroumov, Alexey, Kimmey, Blake A., Taormina, Madison B., Holden, William M., Kim, Kristen, Brown-Mangum, Tiffany, Dani, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983379/
https://www.ncbi.nlm.nih.gov/pubmed/29617674
http://dx.doi.org/10.1016/j.celrep.2018.03.030
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author Thomas, Alyse M.
Ostroumov, Alexey
Kimmey, Blake A.
Taormina, Madison B.
Holden, William M.
Kim, Kristen
Brown-Mangum, Tiffany
Dani, John A.
author_facet Thomas, Alyse M.
Ostroumov, Alexey
Kimmey, Blake A.
Taormina, Madison B.
Holden, William M.
Kim, Kristen
Brown-Mangum, Tiffany
Dani, John A.
author_sort Thomas, Alyse M.
collection PubMed
description Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol were measured 1 month later. We found that adolescent, but not adult, nicotine exposure altered GABA signaling within the ventral tegmental area (VTA) and led to a long-lasting enhancement of alcohol self-administration. We detected depolarizing shifts in GABA(A) reversal potentials arising from impaired chloride extrusion in VTA GABA neurons. Alterations in GABA signaling were dependent on glucocorticoid receptor activation and were associated with attenuated dopaminergic neuron responses to alcohol in the lateral VTA. Importantly, enhancing chloride extrusion in adolescent nicotine-treated animals restored VTA GABA signaling and alcohol self-administration to control levels. Taken together, this work suggests that adolescent nicotine exposure increases the risk profile for increased alcohol drinking in adulthood.
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spelling pubmed-59833792018-06-01 Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration Thomas, Alyse M. Ostroumov, Alexey Kimmey, Blake A. Taormina, Madison B. Holden, William M. Kim, Kristen Brown-Mangum, Tiffany Dani, John A. Cell Rep Article Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol were measured 1 month later. We found that adolescent, but not adult, nicotine exposure altered GABA signaling within the ventral tegmental area (VTA) and led to a long-lasting enhancement of alcohol self-administration. We detected depolarizing shifts in GABA(A) reversal potentials arising from impaired chloride extrusion in VTA GABA neurons. Alterations in GABA signaling were dependent on glucocorticoid receptor activation and were associated with attenuated dopaminergic neuron responses to alcohol in the lateral VTA. Importantly, enhancing chloride extrusion in adolescent nicotine-treated animals restored VTA GABA signaling and alcohol self-administration to control levels. Taken together, this work suggests that adolescent nicotine exposure increases the risk profile for increased alcohol drinking in adulthood. 2018-04-03 /pmc/articles/PMC5983379/ /pubmed/29617674 http://dx.doi.org/10.1016/j.celrep.2018.03.030 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Thomas, Alyse M.
Ostroumov, Alexey
Kimmey, Blake A.
Taormina, Madison B.
Holden, William M.
Kim, Kristen
Brown-Mangum, Tiffany
Dani, John A.
Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title_full Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title_fullStr Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title_full_unstemmed Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title_short Adolescent Nicotine Exposure Alters GABA(A) Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
title_sort adolescent nicotine exposure alters gaba(a) receptor signaling in the ventral tegmental area and increases adult ethanol self-administration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983379/
https://www.ncbi.nlm.nih.gov/pubmed/29617674
http://dx.doi.org/10.1016/j.celrep.2018.03.030
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