Role of interplay between endocannabinoids and neuropeptides in pathogenesis and therapy of depressive and anxiety disorders.

Abstract

A growing body of evidence suggests the existence of a neurochemical and functional interplay between endocannabinoids and neuropeptides, which are both relevant for the pathomechanism and effects of pharmacotherapy in depressive and anxiety disorders. Here, we review the available data on how endocannabinoids influence the activity of the neuropeptidergic systems and conversely, how neuropeptides affect the endocannabinoid system. The explicit/implicit interactions in the relationship of endocannabinoids-neuropeptides are presented. Our paper focuses on both well-known neuropeptides, i.e., corticotropin-releasing hormone/factor, CRH/CRF; oxytocin, OT; arginine-vasopressin, AVP; neuropeptide Y, NPY; orexins/hypocretins, OXs/HCRTs) and less investigated neuropeptides, i.e., nesfatin-1, NEFA; phoenixin, PNX; spexin, SPX; neuropeptide S, NPS). Of all of the brain regions that have been studied, the direct and indirect bidirectional interactions between endocannabinoids and the neuropeptides has most clearly been established in the hypothalamus. It has been proven that neuropeptides are modulators of the multifaceted effects of the endocannabinoid system, namely, its influence on neuroendocrine (CRH/CRF) and behavioral stress responsivity (CRH/CRF, OXs), sociability (OT), feelings of pleasure (OXs/HCRTs, NPS), appetite control (NPY, OXs/HCRTs, CRH/CRF, NEFA) and nociception (OT). This latter effect has only the desirable support of positive influence of endocannabinoids on emotional homeostasis to some extent. Nowadays, increasing attention is being paid to the interplay between endocannabinoids and the less explored peptides, especially NEFA and NPS. This trend is both desirable and necessary for gaining a better understanding of the neurochemical aspects and for providing new insights into the potential therapeutic implications in the treatment of affective disorders.