The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Patkar, Omkar L., Belmer, Arnauld, Holgate, Joan Y., Tarren, Josephine R., Shariff, Masroor R., Morgan, Michael, Fogarty, Matthew J., Bellingham, Mark C., Bartlett, Selena E., & Klenowski, Paul M. (2016) The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice. Addiction Biology. (In Press)

View at publisher

Abstract

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12 weeks) binge ethanol intake, compared with short-term (4 weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency of BLA principal neurons from long-term ethanol-consuming mice but not naive mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Impact and interest:

0 citations in Scopus
Search Google Scholar™

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: 92232
Item Type: Journal Article
Refereed: Yes
Keywords: alcohol, basolateral amygdala, long-term ethanol consumption, norepinephrine, pindolol, serotonin
DOI: 10.1111/adb.12359
ISSN: 1369-1600
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
Copyright Owner: Copyright 2016 Society for the Study of Addiction
Deposited On: 22 Jan 2016 01:27
Last Modified: 05 Oct 2016 01:45

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page