H Plan (2016M3C7A1904988) through the National Investigation Foundation of Korea funded by the Ministry of Science, ICT and Future Arranging. The authors thank Dr. Oh-Sang Kwon for assistance on the evaluation of behavioral information and Do-Hyoung Park for copy editing.SUPPLEMENTARY MATERIALThe Supplementary Material for this article could be located on line at: http:journal.frontiersin.orgarticle10.3389fnhum.2017.000 08full#supplementary-materialREVIEW ARTICLEpublished: 20 December 2013 doi: 10.3389fnins.2013.Cannabinoid-hypocretin cross-talk inside the central nervous system: what we know so farrica Flores , Rafael Maldonado and Fernando Berrendero Laboratory of Neuropharmacology, Division of Experimental and Well being Sciences, Universitat Pompeu Fabra, Barcelona, SpainEdited by: Christopher J. Winrow, Merck, USA Reviewed by: Thomas Heinbockel, Howard University College of Medicine, USA Regina A. Mangieri, The University of Texas at Austin, USA Correspondence: Fernando Berrendero, Laboratory of Neuropharmacology, Division of Experimental and Well being Sciences, Universitat Pompeu Fabra, PRBB, C Physician Aiguader 88, 08003 Barcelona, Spain e-mail: fernando.berrendero@ upf.eduEmerging findings suggest the existence of a cross-talk involving hypocretinergic and endocannabinoid systems. Even though few research have examined this relationship, the apparent overlap observed within the neuroanatomical distribution of both systems as well as their putative Diethyl succinate Purity & Documentation functions strongly point for the existence of such cross-modulation. In agreement, biochemical and functional research have revealed the existence of heterodimers in between CB1 cannabinoid receptor and hypocretin receptor-1, which modulates the cellular localization and downstream signaling of both receptors. In addition, 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 information indicate that endocannabinoids and hypocretins may have prevalent physiological functions in the regulation of appetite, reward and analgesia. In contrast, these neuromodulatory systems seem to play antagonistic roles in the regulation of sleepwake cycle and anxiety-like responses. The present review attempts to piece collectively what is known about this intriguing interaction and describes its potential therapeutic implications.Keywords and phrases: hypocretinergic program, endocannabinoid program, heteromerization, reward, power balance, antinociception, sleepwake cycleENDOCANNABINOIDS AND HYPOCRETINS: TWO Essential NEUROMODULATORSThe extracts of the plant Cannabis sativa include about 60 active compounds of which 9 -tetrahydrocannabinol (THC) would be the key psychoactive component (Hall and Degenhardt, 2009). While it was initially believed that THC exerted its effects by interacting using the plasma membrane Boldenone Cypionate web resulting from its high lipophilic nature (Martin, 1986), the web site of action of this substance is definitely an endogenous neuromodulatory technique termed endogenous cannabinoid technique. The endocannabinoid method is constituted by membrane receptors, their fatty-acid derived endogenous ligands and also the enzymatic machinery that synthesizes and degrades these lipidic neurotransmitters. A minimum of two various cannabinoid receptors happen to be cloned, termed CB1 and CB2 receptors, which share only 44 amino acid (AA) sequence homology (Matsuda et al., 1990; Munro et al., 1993). The distribution of C.