The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption

Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alco...

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Main Authors: Bachtell, Ryan K., Weitemier, Adam Z., Galvan-Rosas, Agustin, Tsivkovskaia, Natalia O., Risinger, Fred O., Phillips, Tamara J., Grahame, Nicholas J., Ryabinin, Andrey E.
Other Authors: Psychiatry, School of Medicine
Format: Article
Language:en_US
Published: Society for Neuroscience 2020
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Online Access:http://hdl.handle.net/1805/21668
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spelling iupuis-1805-216682020-03-06T19:23:35Z The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption Bachtell, Ryan K. Weitemier, Adam Z. Galvan-Rosas, Agustin Tsivkovskaia, Natalia O. Risinger, Fred O. Phillips, Tamara J. Grahame, Nicholas J. Ryabinin, Andrey E. Psychiatry, School of Medicine Urocortin Ethanol Edinger-Westphal Septum Inducible transcription factor Self-administration Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5% ethanol/10% sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the lateral septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW–LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW–LS Ucn pathway in alcohol consumption. 2020-01-01T21:08:24Z 2020-01-01T21:08:24Z 2003-03 Article Bachtell, R. K., Weitemier, A. Z., Galvan-Rosas, A., Tsivkovskaia, N. O., Risinger, F. O., Phillips, T. J., … Ryabinin, A. E. (2003). The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption. The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(6), 2477–2487. doi:10.1523/JNEUROSCI.23-06-02477.2003 http://hdl.handle.net/1805/21668 en_US 10.1523/JNEUROSCI.23-06-02477.2003 The Journal of Neuroscience http://creativecommons.org/licenses/by/4.0/ Society for Neuroscience PMC
institution IUPUIScholarWorks
collection DSpace
language en_US
topic Urocortin
Ethanol
Edinger-Westphal
Septum
Inducible transcription factor
Self-administration
spellingShingle Urocortin
Ethanol
Edinger-Westphal
Septum
Inducible transcription factor
Self-administration
Bachtell, Ryan K.
Weitemier, Adam Z.
Galvan-Rosas, Agustin
Tsivkovskaia, Natalia O.
Risinger, Fred O.
Phillips, Tamara J.
Grahame, Nicholas J.
Ryabinin, Andrey E.
The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
description Identifying and characterizing brain regions regulating alcohol consumption is beneficial for understanding the mechanisms of alcoholism. To this aim, we first identified brain regions changing in expression of the inducible transcription factor c-Fos in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) mice after ethanol consumption. Drinking a 5% ethanol/10% sucrose solution in a 30 min limited access procedure led to induction of c-Fos immunoreactivity in urocortin (Ucn)-positive cells of the Edinger-Westphal nucleus (EW), suppression of c-Fos immunoreactivity in the dorsal portion of the lateral septum (LS) of both strains of mice, and strain-specific suppression in the intermediate portion of the LS and the CA3 hippocampal region. Because the EW sends Ucn projections to the LS, and B6 and D2 mice differ dramatically in EW Ucn expression, we further analyzed the Ucn EW–LS pathway using several genetic approaches. We find that D2 mice have higher numbers of Ucn-immunoreactive processes than B6 mice in the LS and that consumption of ethanol/sucrose in the F2 offspring of a B6D2 intercross positively correlates with Ucn immunoreactivity in the EW and negatively correlates with Ucn immunoreactivity in the LS. In agreement with these findings, we find that alcohol-avoiding male B6.D2Alcp1 line 2.2 congenic mice have lower Ucn immunoreactivity in the EW than male B6.B6 mice. Finally, we also find that HAP mice, selectively bred for high alcohol preference, have higher Ucn immunoreactivity in EW, than LAP mice, selectively bred for low alcohol preference. Taken together, these studies provide substantial evidence for involvement of the EW–LS Ucn pathway in alcohol consumption.
author2 Psychiatry, School of Medicine
author_facet Psychiatry, School of Medicine
Bachtell, Ryan K.
Weitemier, Adam Z.
Galvan-Rosas, Agustin
Tsivkovskaia, Natalia O.
Risinger, Fred O.
Phillips, Tamara J.
Grahame, Nicholas J.
Ryabinin, Andrey E.
format Article
author Bachtell, Ryan K.
Weitemier, Adam Z.
Galvan-Rosas, Agustin
Tsivkovskaia, Natalia O.
Risinger, Fred O.
Phillips, Tamara J.
Grahame, Nicholas J.
Ryabinin, Andrey E.
author_sort Bachtell, Ryan K.
title The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
title_short The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
title_full The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
title_fullStr The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
title_full_unstemmed The Edinger-Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
title_sort edinger-westphal-lateral septum urocortin pathway and its relationship to alcohol consumption
publisher Society for Neuroscience
publishDate 2020
url http://hdl.handle.net/1805/21668
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