期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 183, 期 -, 页码 22-31出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2019.06.007
关键词
Conditioned place preference; Alcohol; Endocannabinoids; CB2R cannabinoid receptors
资金
- Ministerio de Economia y Competitividad (Spanish Ministry of Healthby Ministerio de Sanidad, Servicios Sociales e Igualdad) [SAF2016-75966-R-FEDER]
- Spanish Ministry of Health [Relic-ISCIII-RD16/0017/0010]
- Spanish Ministry of Health (Plan Nacional sobre Drogas) [2018/007]
- Conselleria d'Educacio, Investigacio, Cultura i Esport (APOSTD/2017), Generalitat Valenciana, Spain
- MINECO [MDM-2014-0370]
The endocannabinoid (eCB) system is a particularly important neuronal mechanism implicated in alcohol use disorders. Animal models are key to broadening our knowledge of the neurobiological mechanisms underlying alcohol dependence. This study has two main aims: i) to assess how eCB levels in different brain areas are modified by alcohol-induced conditioning place preference (CPP), and ii) to study how cannabinoid type 2 receptor (CB2R) is involved in alcohol-rewarding properties, using pharmacological manipulation in C57BL/6 mice. Our results suggest that the eCB system is dysregulated throughout the mesocorticolimbic system by repeated alcohol exposure during the CPP paradigm, and that levels of anandamide (AEA) and several other N-acylethanolamines are markedly decreased in the medial prefrontal cortex and ventral midbrain of alcohol-CPP mice. We also observed that the administering an antagonist/inverse agonist of the CB2R (AM630) during the acquisition phase of CPP reduced the rewarding effects of alcohol. However, activating CB2R signalling using the agonist JVVH133 seems to reduce both alcohol-and food-rewarding behaviours. Therefore, our findings indicate that the rewarding effects of alcohol are related to its disruptive effect on AEA and other N-acylethanolamine signalling pathways. Thus, pharmacological manipulation of CB2R is an interesting candidate treatment for alcohol use disorders.
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