دورية أكاديمية
Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.
| العنوان: | Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity. |
|---|---|
| المؤلفون: | Vilela LR; Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Gobira PH; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Viana TG; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Medeiros DC; Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Ferreira-Vieira TH; Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Doria JG; Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Rodrigues F; Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Aguiar DC; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Pereira GS; Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Massessini AR; Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Ribeiro FM; Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Oliveira AC; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Moraes MF; Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: mfdm@icb.ufmg.br., Moreira FA; Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: fabriciomoreira@icb.ufmg.br. |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2015 Aug 01; Vol. 286 (3), pp. 178-87. Date of Electronic Publication: 2015 Apr 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Cocaine/*toxicity , Endocannabinoids/*metabolism , Receptor, Cannabinoid, CB1/*metabolism , Signal Transduction/*drug effects, Animals ; Benzamides/pharmacology ; Carbamates/pharmacology ; Cell Death/drug effects ; Cell Death/physiology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Endocannabinoids/agonists ; Hippocampus/drug effects ; Hippocampus/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Receptor, Cannabinoid, CB1/agonists ; Signal Transduction/physiology |
| مستخلص: | Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. (Copyright © 2015 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Anandamide; Cocaine; Endocannabinoid; FAAH; PI3K; Seizures |
| المشرفين على المادة: | 0 (Benzamides) 0 (Carbamates) 0 (Endocannabinoids) 0 (Neuroprotective Agents) 0 (Receptor, Cannabinoid, CB1) 0 (cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester) I5Y540LHVR (Cocaine) |
| تواريخ الأحداث: | Date Created: 20150503 Date Completed: 20150817 Latest Revision: 20150608 |
| رمز التحديث: | 20230127 |
| DOI: | 10.1016/j.taap.2015.04.013 |
| PMID: | 25933444 |
| قاعدة البيانات: | MEDLINE |
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