Flores de los Heros, África, 1985-Maldonado, Rafael, 1961-Berrendero Díaz, Fernando, 1971-2015-03-232015-03-232013Flores A, Maldonado R, Berrendero F. Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far. Front Neurosci. 2013 Dec 20;7:256. DOI: 10.3389/fnins.2013.002561662-4548http://hdl.handle.net/10230/23254Emerging findings suggest the existence of a cross-talk between hypocretinergic and endocannabinoid systems. Although few studies have examined this relationship, the apparent overlap observed in the neuroanatomical distribution of both systems as well as their putative functions strongly point to the existence of such cross-modulation. In agreement, biochemical and functional studies have revealed the existence of heterodimers between CB1 cannabinoid receptor and hypocretin receptor-1, which modulates the cellular localization and downstream signaling of both receptors. Moreover, the activation of hypocretin receptor-1 stimulates the synthesis of 2-arachidonoyl glycerol culminating in the retrograde inhibition of neighboring cells and suggesting that endocannabinoids could contribute to some hypocretin effects. Pharmacological data indicate that endocannabinoids and hypocretins might have common physiological functions in the regulation of appetite, reward and analgesia. In contrast, these neuromodulatory systems seem to play antagonistic roles in the regulation of sleep/wake cycle and anxiety-like responses. The present review attempts to piece together what is known about this interesting interaction and describes its potential therapeutic implications.application/pdfeng© 2013 África Flores, Rafael Madonado and Fernando Berrendero Díaz. This is an open-access article distributed under the terms of a Creative Commons Attribution License(CCBY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or/nreproduction is permitted which does not comply with these termsSistema nerviós centralCannabinoidesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fnins.2013.00256info:eu-repo/semantics/openAccess