TY - JOUR
T1 - Role of the area postrema in the hypophagic effects of oleoylethanolamide
AU - Romano, Adele
AU - Gallelli, Cristina Anna
AU - Koczwara, Justyna Barbara
AU - Braegger, Fiona E.
AU - Vitalone, Annabella
AU - Falchi, Mario
AU - Micioni Di Bonaventura, Maria Vittoria
AU - Cifani, Carlo
AU - Cassano, Tommaso
AU - Lutz, Thomas A.
AU - Gaetani, Silvana
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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. Visceral ascending fibers were hypothesized to mediate such 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. 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. 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. These results support the hypothesis of a necessary role of the AP in mediating OEA's central effects that sustain its pro-satiety action.
AB - 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. Visceral ascending fibers were hypothesized to mediate such 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. 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. 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. These results support the hypothesis of a necessary role of the AP in mediating OEA's central effects that sustain its pro-satiety action.
KW - Area postrema
KW - Brainstem
KW - Feeding behavior
KW - Hypothalamus
KW - Nucleus of the solitary tract
KW - Satiety
UR - http://www.scopus.com/inward/record.url?scp=85019742233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019742233&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2017.05.017
DO - 10.1016/j.phrs.2017.05.017
M3 - Article
C2 - 28535974
AN - SCOPUS:85019742233
VL - 122
SP - 20
EP - 34
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
ER -