Envolvimento do sistema endocanabinoide na modulação de crises convulsivas experimentais

Abstract

In the present study we investigated the involvement of the endocannabinoid and endovaniloid systems in animal models of chemically-induced seizures by pentylenetetrazole (PTZ) and cocaine overdose. Animals were treated, prior to administration of convulsant agents, with compounds such as CB1 agonists or antagonists, FAAH inhibitor (which hydrolyzes the endocannabinoid anandamide) and the dual inhibitor of FAAH/TRPV1 (vanilloid receptor). We evaluated parameters related to behavioral and electroencephalographic (EEG) seizure, in addition to cell death in the hippocampus. The results show that CB1 agonists and antagonists induced contradictory or negative effect in PTZ and cocaine overdose models, whereas the increase in endocanabinoid signaling through FAAH inhibition induced anticonvulsant effects. In addition, the FAAH inhibitor prevented the neuronal death observed in vivo and in vitro after cocaine-induced seizures, representing neuroprotective strategy. The results also show that increasing the endocannabinoid signaling, associated with the TRPV1 receptor blockade (dual FAAH/TRPV1 blocker), promotes anticonvulsant effect in the PTZ model in mice. The interaction between the endocannabinoid and endovaniloid system are relevant in the seizure modulation, representing an additional strategy for the development of new anticonvulsant drugs.