High Fat Diet Bingeing Activates the Mesolimbic Circuit and Requires the Orexin Signaling

SPRING VALDIVIA; ANABELA PATRONE; MIRTA REYNALDO; MARIO PERELLO

Congreso; XXVIII congreso de la SAN; 2013

Many people suffering eating disorders display binge eating episodes, in which an excessive amount of palatable foods is rapidly consumed. Currently, little is known about the neuronal circuitries recruited by the acute ingestion of a rewarding stimulus. Here, we used a combination of immunohistochemistry, pharmacology and neuronal tracing analyses to examine the role of the mesolimbic system, in general, and the orexin neurons, in particular, in a simple experimental paradigm in which naïve mice are allowed to spontaneously eat a pellet of a high fat diet (HFD) for 2 h. We found that acute HF intake activates c-Fos expression in several reward-related brain areas. We also found that: i-HFD-mediated orosensory stimulation was required for the mesolimbic pathway activation, ii-acute HF intake activates dopaminergic neurons of the paranigral, parabrachial pigmented and interfascicular sub-regions of the ventral tegmental area (VTA); and iii-orexin neurons of the lateral hypothalamus (LHA) are responsive to acute HF intake. In addition, we found that orexin signaling blockage, with the orexin 1 receptor antagonist SB-334867, reduces acute HF intake and c-Fos induction in the VTA but not in other mesolimbic nuclei. Finally, we found that most orexin neurons responsive to acute HF intake innervate the VTA. Our results show that HFD binge recruits the mesolimbic system and that the manifestation of this eating behavior requires activation of the orexin signaling.