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Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence

BACKGROUND: Alcohol has been shown to critically modulate cyclic adenosine-3′,5′ monophosphate (cAMP) signaling. A number of downstream effectors that respond to the cAMP signals (e.g., protein kinase A, cAMP response element binding protein) have, in turn, been examined in relation to alcohol consu...

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Autores principales: Desrivières, Sylvane, Pronko, Sergey P., Lourdusamy, Anbarasu, Ducci, Francesca, Hoffman, Paula L., Wodarz, Norbert, Ridinger, Monika, Rietschel, Marcella, Zelenika, Diana, Lathrop, Mark, Schumann, Gunter, Tabakoff, Boris
Formato: Texto
Lenguaje:English
Publicado: Elsevier 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094753/
https://www.ncbi.nlm.nih.gov/pubmed/21481845
http://dx.doi.org/10.1016/j.biopsych.2011.01.037
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author Desrivières, Sylvane
Pronko, Sergey P.
Lourdusamy, Anbarasu
Ducci, Francesca
Hoffman, Paula L.
Wodarz, Norbert
Ridinger, Monika
Rietschel, Marcella
Zelenika, Diana
Lathrop, Mark
Schumann, Gunter
Tabakoff, Boris
author_facet Desrivières, Sylvane
Pronko, Sergey P.
Lourdusamy, Anbarasu
Ducci, Francesca
Hoffman, Paula L.
Wodarz, Norbert
Ridinger, Monika
Rietschel, Marcella
Zelenika, Diana
Lathrop, Mark
Schumann, Gunter
Tabakoff, Boris
author_sort Desrivières, Sylvane
collection PubMed
description BACKGROUND: Alcohol has been shown to critically modulate cyclic adenosine-3′,5′ monophosphate (cAMP) signaling. A number of downstream effectors that respond to the cAMP signals (e.g., protein kinase A, cAMP response element binding protein) have, in turn, been examined in relation to alcohol consumption. These studies did not, however, delineate the point at which the actions of alcohol on the cAMP cascade might translate into differences in drinking behavior. To further understand the role of cAMP synthesis in alcohol drinking and dependence, we investigated a specific adenylyl cyclase isoform, adenylyl cyclase (AC) Type 7, whose activity is selectively enhanced by ethanol. METHODS: We measured alcohol consumption and preference in mice in which one copy of the Adcy7 gene was disrupted (Adcy7(+/−)). To demonstrate relevance of this gene for alcohol dependence in humans, we tested the association of polymorphisms in the ADCY7 gene with alcohol dependence in a sample of 1703 alcohol-dependent individuals and 1347 control subjects. RESULTS: We show that Adcy7(+/−) female mice have higher preference for alcohol than wild-type mice, whereas there is little difference in alcohol consumption or preference between Adcy7(+/−) male mice and wild-type control subjects. In the human sample, we found that single nucleotide polymorphisms in ADCY7 associate with alcohol dependence in women, and these markers are also associated with ADCY7 expression (messenger RNA) levels. CONCLUSIONS: These findings implicate adenylyl cyclase Type 7 as a critical component of the molecular pathways contributing to alcohol drinking and the development of alcohol dependence.
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spelling pubmed-30947532011-07-12 Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence Desrivières, Sylvane Pronko, Sergey P. Lourdusamy, Anbarasu Ducci, Francesca Hoffman, Paula L. Wodarz, Norbert Ridinger, Monika Rietschel, Marcella Zelenika, Diana Lathrop, Mark Schumann, Gunter Tabakoff, Boris Biol Psychiatry Archival Report BACKGROUND: Alcohol has been shown to critically modulate cyclic adenosine-3′,5′ monophosphate (cAMP) signaling. A number of downstream effectors that respond to the cAMP signals (e.g., protein kinase A, cAMP response element binding protein) have, in turn, been examined in relation to alcohol consumption. These studies did not, however, delineate the point at which the actions of alcohol on the cAMP cascade might translate into differences in drinking behavior. To further understand the role of cAMP synthesis in alcohol drinking and dependence, we investigated a specific adenylyl cyclase isoform, adenylyl cyclase (AC) Type 7, whose activity is selectively enhanced by ethanol. METHODS: We measured alcohol consumption and preference in mice in which one copy of the Adcy7 gene was disrupted (Adcy7(+/−)). To demonstrate relevance of this gene for alcohol dependence in humans, we tested the association of polymorphisms in the ADCY7 gene with alcohol dependence in a sample of 1703 alcohol-dependent individuals and 1347 control subjects. RESULTS: We show that Adcy7(+/−) female mice have higher preference for alcohol than wild-type mice, whereas there is little difference in alcohol consumption or preference between Adcy7(+/−) male mice and wild-type control subjects. In the human sample, we found that single nucleotide polymorphisms in ADCY7 associate with alcohol dependence in women, and these markers are also associated with ADCY7 expression (messenger RNA) levels. CONCLUSIONS: These findings implicate adenylyl cyclase Type 7 as a critical component of the molecular pathways contributing to alcohol drinking and the development of alcohol dependence. Elsevier 2011-06-01 /pmc/articles/PMC3094753/ /pubmed/21481845 http://dx.doi.org/10.1016/j.biopsych.2011.01.037 Text en © 2011 Elsevier Inc. https://creativecommons.org/licenses/by/4.0/ Open Access under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) license
spellingShingle Archival Report
Desrivières, Sylvane
Pronko, Sergey P.
Lourdusamy, Anbarasu
Ducci, Francesca
Hoffman, Paula L.
Wodarz, Norbert
Ridinger, Monika
Rietschel, Marcella
Zelenika, Diana
Lathrop, Mark
Schumann, Gunter
Tabakoff, Boris
Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title_full Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title_fullStr Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title_full_unstemmed Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title_short Sex-Specific Role for Adenylyl Cyclase Type 7 in Alcohol Dependence
title_sort sex-specific role for adenylyl cyclase type 7 in alcohol dependence
topic Archival Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094753/
https://www.ncbi.nlm.nih.gov/pubmed/21481845
http://dx.doi.org/10.1016/j.biopsych.2011.01.037
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