The hypothalamic endocannabinoid system participates in the secretion of oxytocin and tumor necrosis factor-alpha induced by lipopolysaccharide

This study investigated the participation of the hypothalamic endocannabinoid system in the response to lipopolysaccharide (LPS) challenge evaluating oxytocin (OXT) and tumor necrosis factor-alpha (TNF-a) plasma levels in vivo and their release from hypothalamic fragments in vitro. LPS increased OXT and TNF-α release through anandamide-activation of hypothalamic cannabinoid receptor CB1, since the antagonist AM251 blocked this effect. Anandamide, through its receptors, also increased hypothalamic nitric oxide (NO) which inhibited OXT release, ending the stimulatory effect of the endocannabinoid. Our findings reveal a hypothalamic interaction between oxytocin, endocannabinoid and NO-ergic systems providing a regulation of the hypothalamic–neurohypophyseal axis under basal and stress conditions.