scholarly journals Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models

Author(s):  
Nathan D. Winters ◽  
Gaurav Bedse ◽  
Anastasia A. Astafyev ◽  
Toni A. Patrick ◽  
Megan Altemus ◽  
...  
2021 ◽  
Author(s):  
Gaurav Bedse ◽  
Nathan D. Winters ◽  
Anastasia Astafyev ◽  
Toni A. Patrick ◽  
Vikrant R. Mahajan ◽  
...  

ABSTRACTAlcohol use disorder (AUD) is associated with substantial morbidity, mortality, and societal cost, and pharmacological treatment options for AUD are limited. The endogenous cannabinoid (eCB) signaling system is critically involved in reward processing and alcohol intake is positively correlated with release of the eCB ligand 2-Arachidonoylglycerol (2-AG) within reward neurocircuitry. Here we show that genetic and pharmacological inhibition of diacylglycerol lipase (DAGL), the rate limiting enzyme in the synthesis of 2-AG, reduces alcohol consumption in a variety of preclinical models ranging from a voluntary free-access model to aversion resistant-drinking, and dependence-like drinking induced via chronic intermittent ethanol vapor exposure in mice. DAGL inhibition also prevented ethanol-induced suppression of GABAergic transmission onto midbrain dopamine neurons, providing mechanistic insight into how DAGL inhibition could affect alcohol reward. Lastly, DAGL inhibition during either chronic alcohol consumption or protracted withdrawal was devoid of anxiogenic and depressive-like behavioral effects. These data suggest reducing 2-AG signaling via inhibition of DAGL could represent a novel approach to reduce alcohol consumption across the spectrum of AUD severity.


2001 ◽  
Vol 120 (5) ◽  
pp. A117-A117
Author(s):  
K DEAR ◽  
M BRADLEY ◽  
K MCCORMACK ◽  
R PECK ◽  
D GLEESON

2008 ◽  
Vol 7 ◽  
pp. 20-20
Author(s):  
G LEVANTESI ◽  
R MARFISI ◽  
M SCARANO ◽  
M SILLETTA ◽  
A MAGGIONI ◽  
...  

Crisis ◽  
2016 ◽  
Vol 37 (3) ◽  
pp. 232-235 ◽  
Author(s):  
Christopher R. DeCou ◽  
Monica C. Skewes

Abstract. Background: Previous research has demonstrated an association between alcohol-related problems and suicidal ideation (SI). Aims: The present study evaluated, simultaneously, alcohol consequences and symptoms of alcohol dependence as predictors of SI after adjusting for depressive symptoms and alcohol consumption. Method: A sample of 298 Alaskan undergraduates completed survey measures, including the Young Adult Alcohol Consequences Questionnaire, the Short Alcohol Dependence Data Questionnaire, and the Beck Depression Inventory – II. The association between alcohol problems and SI status was evaluated using sequential logistic regression. Results: Symptoms of alcohol dependence (OR = 1.88, p < .05), but not alcohol-related consequences (OR = 1.01, p = .95), emerged as an independent predictor of SI status above and beyond depressive symptoms (OR = 2.39, p < .001) and alcohol consumption (OR = 1.08, p = .39). Conclusion: Alcohol dependence symptoms represented a unique risk for SI relative to alcohol-related consequences and alcohol consumption. Future research should examine the causal mechanism behind the relationship between alcohol dependence and suicidality among university students. Assessing the presence of dependence symptoms may improve the accuracy of identifying students at risk of SI.


Author(s):  
Colleen S. Rand ◽  
Brian A. Lawlor ◽  
John M. Kuldau

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