Role of the area postrema in the hypophagic effects of oleoylethanolamide

Introduction The satiety-promoting action of oleoylethanolamide (OEA) has been associated to the indirect activation of selected brain areas, such as the nucleus of the solitary tract (NST) in the brainstem and the tuberomammillary (TMN) and paraventricular (PVN) nuclei in the hypothalamus, where noradrenergic, histaminergic and oxytocinergic neurons play a necessary role. Aim Visceral ascending fibers were hypothesized to mediate OEA’s effects. However, our previous findings demonstrated that the hypophagic action of peripherally administered OEA does not require intact vagal afferents and is associated to a strong activation of the area postrema (AP). Therefore, we hypothesized that OEA may exert its central effects through the direct activation of this circumventricular organ. Methods To test this hypothesis, we subjected rats to the surgical ablation of the AP (APX rats) and evaluated the effects of OEA (10 mg kg-1 i.p.) on food intake, Fos expression, hypothalamic oxytocin (OXY) immunoreactivity and on the expression of dopamine beta hydroxylase (DBH) in the brainstem and hypothalamus. SHAM-operated animals (SHAM rats) were used as controls. Results We found that the AP lesion completely prevented OEA’s behavioral and neurochemical effects in the brainstem and the hypothalamus. Moreover OEA increased DBH expression in AP and NST neurons of SHAM rats while the effect in the NST was absent in APX rats, thus suggesting the possible involvement of noradrenergic AP neurons. Conclusion Our results support the hypothesis of a necessary role of the AP in mediating OEA’s central effects that sustain its pro-satiety action. Funding source: this work was supported by a grant (PRIN 2012JTX3KL to CC and SG) of the Italian Ministry of Education, University and Research.The authors declare no actual or potential conflicts of interest