Modulators of endogenous cannabinoid system аs neuroprotectors

Abstract

The neuroprotective action of endocannabinoid N-arachidonoyldopamine(AA-DA) in the model of apoptosis induced incultured rat cerebellar granule neurons by K+ deprivation wasinvestigated. The efficacy of simultaneous application of AA-DAwith fatty acid amide hydrolase inhibitor N-eicosapentaenoyldopamine(EPA-5HT) was also evaluated. It was shown thatAA-DA dose-dependently protects neurons, with maximaleffect of 65% survived cells observed at concentration 10 M.The use of submaximal concentration (5 M) of AA-DA incombination with EPA-5HT (10 M) led to significantenhancement of neuroprotection. The value of cell survival forthe combination exceeded such values for AA-DA alone in concentrationof 5 and 10 M, increasing the neuronal survival up to78%. It may be concluded that such combination allows toreduce efficient concentration of neuroprotector and to diminishits possible side effects. Thus, the simultaneous application ofendocannabinoid system modulators such as cannabinoidreceptor agonists and inhibitors of endocannabinoid hydrolysisappears to be effective approach for neural cells protection.

Keywords

• neuroprotection
• endocannabinoids
• n-arachidonoyldopamine
• anandamide
• fatty acid amide hydrolase
• apoptosis
• cerebellar granule neurons