Endocannabinoid contributions to alcohol habits and motivation: relevance to treatment
| Autor: | Mario van der Stelt, Ming Jiang, Stephanie M. Groman, Jane R. Taylor, Carol A. Gianessi, Summer L. Thompson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Alcohol Drinking
Drug-Seeking Behavior Medicine (miscellaneous) Alcohol Alcohol use disorder Arachidonic Acids Pharmacology Article Glycerides 03 medical and health sciences chemistry.chemical_compound Habits Mice 0302 clinical medicine Piperidines Receptor Cannabinoid CB1 Cannabinoid receptor type 1 Medicine Animals Benzodioxoles Cannabinoid Receptor Antagonists JZL184 Motivation Ethanol business.industry Central Nervous System Depressants Transport inhibitor medicine.disease Endocannabinoid system Monoacylglycerol Lipases 030227 psychiatry Psychiatry and Mental health Lipoprotein Lipase chemistry AM404 Pyrazoles lipids (amino acids peptides and proteins) business Lithium Chloride 030217 neurology & neurosurgery Endocannabinoids |
| Zdroj: | Addict Biol Addiction Biology Addiction Biology, 25(3), e12768 |
| Popis: | Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown. Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice. We found that administration of the novel diacyl glycerol lipase inhibitor DO34, which decreases the biosynthesis of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced habitual responding for ethanol and ethanol approach behaviors. Moreover, administration of the endocannabinoid transport inhibitor AM404 or the cannabinoid receptor type 1 antagonist AM251 produced similar reductions in habitual responding for ethanol and ethanol approach behaviors. Notably, AM404 was also able to reduce ethanol seeking and consumption in mice that were insensitive to lithium chloride-induced devaluation of ethanol. Conversely, administration of JZL184, a monoacyl glycerol lipase inhibitor that increases levels of 2-AG, increased motivation to respond for ethanol on a progressive ratio schedule of reinforcement. These results demonstrate an important role for endocannabinoid signaling in the motivation to seek ethanol, in ethanol-motivated habits, and suggest that pharmacological manipulations of endocannabinoid signaling could be effective therapeutics for treating alcohol use disorder. |
| Databáze: | OpenAIRE |
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