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dc.contributor.authorLiput, D.J.
dc.contributor.authorPauly, J.R.
dc.contributor.authorStinchcomb, A.L.
dc.date.accessioned2019-07-15T16:12:14Z
dc.date.available2019-07-15T16:12:14Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85037644017&doi=10.3390%2fbrainsci7120158&partnerID=40&md5=3f53a49067db4244ce8662767bfbc360
dc.identifier.urihttp://hdl.handle.net/10713/9955
dc.description.abstractExcessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in [3H]-CP-55,940 binding in the entorhinal cortex and hippocampus following two days, but not four days, of treatment. Furthermore, binge alcohol treatment did not change the tissue content of the three NAEs quantified, including the endocannabinoid and anandamide. In a separate study, the FAAH inhibitor, URB597 was administered to rats during alcohol treatment and neuroprotection was assessed by FluoroJade B (FJB) staining. The administration of URB597 during binge treatment did not significantly reduce FJB+ cells in the entorhinal cortex or hippocampus, however, a follow up "target engagement" study found that NAE augmentation by URB597 was impaired in alcohol intoxicated rats. Thus, potential alcohol induced alterations in URB597 pharmacodynamics may have contributed to the lack of neuroprotection by FAAH inhibition. Copyright 2017 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipThe authors thank Deann Hopkins and Dana Hammell for their excellent technical support pertaining to CB1 receptor binding and endocannabinoid quantification, respectively. The work described was funded by NIH R01AA016959 (KN), F31AA019853 (DJL), T32DA016176 (DJL) and R41AA016499 (KN/ALS).en_US
dc.description.urihttps://www.doi.org/10.3390/brainsci7120158en_US
dc.language.isoen_USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofBrain Sciences
dc.subjectAlcoholen_US
dc.subjectAlcoholismen_US
dc.subjectCB1en_US
dc.subjectEndocannabinoiden_US
dc.subjectEthanolen_US
dc.subjectFAAHen_US
dc.subjectN-acylethanolamineen_US
dc.subjectNeurodegenerationen_US
dc.titleBinge alcohol exposure transiently changes the endocannabinoid system: A potential target to prevent alcohol-induced neurodegenerationen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/brainsci7120158


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