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The antihypertensive drug pindolol attenuates long‐term but not short‐term binge‐like ethanol consumption in mice
Author(s) -
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.
Publication year - 2017
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12359
Subject(s) - pindolol , pharmacology , ethanol , binge drinking , addiction , partial agonist , antagonist , alcohol , chemistry , medicine , endocrinology , psychology , receptor , neuroscience , alcohol consumption , biochemistry
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‐HT 1A/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 naïve mice. Additionally, this effect was blocked by the 5‐HT 1A/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.