2-Arachidonoylglycerol endocannabinoid signaling coupled to metabotropic glutamate receptor type-5 modulates anxiety-like behavior in the rat ventromedial prefrontal cortex

Autor(es)

Almeida-Santos, Ana F. ; Moreira, Fabricio A. ; Guimaraes, Francisco S. ; Aguiar, Daniele C.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PSYCHOPHARMACOLOGY; v. 31, n. 6, p. 740-749, JUN 2017.
• Citações Web of Science: 3

Resumo

2-Arachidonoylglycerol and anandamide are the main endocannabinoids, which act through cannabinoid type-1 and type-2 receptors. Among its many functions, anandamide modulates anxiety-like behaviors in the ventromedial prefrontal cortex. The role of 2-arachidonoylglycerol in this region, however, has remained unclear. Here, we verified whether intra- ventromedial prefrontal cortex injection of 2-arachidonoylglycerol or URB602, a monoacylglycerol lipase inhibitor (responsible for 2-arachidonoylglycerol hydrolysis), induce anxiolytic-like effects in Wistar rats. Since activation of metabotropic glutamate receptor type 5 promotes diacylglycerol lipase--mediated 2-arachidonoylglycerol synthesis, we also verified if the blockade of this receptor impairs the anxiolytic-like effect induced by URB 602. 2-Arachidonoylglycerol reduced anxiety-like response in rats exposed to the Elevated Plus Maze test, an effect mimicked by URB602. Cannabinoid type-1 and type-2 receptor antagonists prevented these effects. The pre-treatment with an ineffective dose of MPEP, a metabotropic glutamate receptor type 5 antagonist, also attenuated the anxiolytic-like effect of URB602. Moreover, immunofluorescence microscopy revealed co-expression of metabotropic glutamate receptor type 5 and diacylglycerol lipase- in several neurons in slices from the ventromedial prefrontal cortex. Altogether, our results implicate 2-arachidonoylglycerol and both cannabinoid receptors on anxiety-related behaviors mediated by ventromedial prefrontal cortex. Further, these data support a role for the coupling between metabotropic glutamate receptor type 5 activation and 2-arachidonoylglycerol signalling as a mechanism modulating aversive responses. (AU)

• Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático