Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor

Carnicella, S., Ahmadiantehrani, S., He, D. Y., Nielsen, C. K., Bartlett, S. E., Janak, P. H., & Ron, D. (2009) Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor. Biological Psychiatry, 66(2), pp. 146-153.

View at publisher (open access)


Background: Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). Results: We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Conclusions: Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders. © 2009 Society of Biological Psychiatry.

Impact and interest:

20 citations in Scopus
Search Google Scholar™
18 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 47757
Item Type: Journal Article
Refereed: Yes
Keywords: Addiction, alcohol, cabergoline, GDNF, growth factor, treatment
DOI: 10.1016/j.biopsych.2008.12.022
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Past > Schools > Pharmacy
Copyright Owner: Elsevier
Deposited On: 15 Dec 2011 01:11
Last Modified: 29 Feb 2012 14:34

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page