The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice.
Addict Biol
; 22(3): 679-691, 2017 May.
Article
in En
| MEDLINE
| ID: mdl-27273539
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 naïve 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pindolol
/
Behavior, Animal
/
Ethanol
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Binge Drinking
/
Antihypertensive Agents
Limits:
Animals
Language:
En
Journal:
Addict Biol
Journal subject:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Year:
2017
Type:
Article
Affiliation country:
Australia