Nucleus incertus corticotrophin-releasing factor 1 receptor signalling regulates alcohol seeking in rats

Walker, Leigh C., Kastman, Hanna E., Koeleman, Jan A., Smith, Craig M., Perry, Christina J., Krstew, Elena V., Gundlach, Andrew L. and Lawrence, Andrew J. 2016, Nucleus incertus corticotrophin-releasing factor 1 receptor signalling regulates alcohol seeking in rats, Addiction biology, doi: 10.1111/adb.12426.

Attached Files
Name Description MIMEType Size Downloads

Title Nucleus incertus corticotrophin-releasing factor 1 receptor signalling regulates alcohol seeking in rats
Author(s) Walker, Leigh C.
Kastman, Hanna E.
Koeleman, Jan A.
Smith, Craig M.
Perry, Christina J.
Krstew, Elena V.
Gundlach, Andrew L.
Lawrence, Andrew J.
Journal name Addiction biology
Total pages 14
Publisher Wiley
Place of publication Hoboken, N.J.
Publication date 2016-07-20
ISSN 1369-1600
Keyword(s) alcohol
corticotrophin-releasing factor
nucleus incertus
Summary Alcoholism is a chronic relapsing disorder, and stress is a key precipitant of relapse. The nucleus incertus (NI) is highly responsive to corticotrophin-releasing factor (CRF) and psychological stressors, receives a CRF innervation and expresses CRF1 and CRF2 receptor mRNA. Furthermore, the ascending NI relaxin-3 system is implicated in alcohol seeking in rats. Therefore, in alcohol-preferring rats, we examined the effect of bilateral injections into the NI of the CRF1 receptor antagonist, CP376395 or the CRF2 receptor antagonist, astressin-2B on yohimbine-induced reinstatement of alcohol seeking. Using quantitative PCR analysis of NI micropunches, we assessed the effects of chronic alcohol consumption on gene expression profiles for components of the relaxin-3 and CRF systems. Bilateral intra-NI injections of CP376395 (500 ng/0.25 µl) attenuated yohimbine-induced reinstatement of alcohol seeking. In contrast, intra-NI injections of astressin-2B (200 ng/0.25 µl) had no significant effect. In line with these data, CRF1 , but not CRF2 , receptor mRNA was upregulated in the NI following chronic ethanol intake. Relaxin family peptide 3 receptor mRNA was also increased in the NI following chronic ethanol. Our quantitative PCR analysis also identified CRF mRNA within the rat NI, and the existence of a newly identified population of CRF-containing neurons was subsequently confirmed by detection of CRF immunoreactivity in rat and mouse NI. These data suggest that NI neurons contribute to reinstatement of alcohol seeking, via an involvement of CRF1 signalling. Furthermore, chronic ethanol intake leads to neuroadaptive changes in CRF and relaxin-3 systems within rat NI.
Notes In press
Language eng
DOI 10.1111/adb.12426
Field of Research 111708 Health and Community Services
Socio Economic Objective 920414 Substance Abuse
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Society for the Study of Addiction
Persistent URL

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 6 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 85 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Fri, 24 Feb 2017, 15:11:08 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact