DMV Extrasynaptic NMDA Receptors Regulate Caloric Intake in Rats.

Acute high fat diet (HFD) exposure induces a brief period of hyperphagia before caloric balance is restored. Previous studies have demonstrated this period of regulation is associated with activation of synaptic NMDA receptors (NMDARs) on dorsal motor nucleus of the vagus (DMV) neurons, which increases vagal control of gastric functions. Our aim was to test the hypothesis that activation of DMV NMDARs occurs subsequent to activation of extrasynaptic NMDA receptors (NMDARex). Sprague-Dawley rats were fed control or HFD for 3-5 days prior to experimentation. Whole cell patch clamp recordings from gastric-projecting DMV neurons, in vivo recordings of gastric motility, tone, compliance, and emptying, as well as food intake studies were used to assess the effects of NMDAR antagonism on caloric regulation. Following acute HFD exposure, inhibition of NMDARex prevented the NMDARs-mediated increase in glutamatergic transmission to DMV neurons, as well as the increase in gastric tone and motility, while chronic NMDARex inhibition attenuated the regulation of caloric intake. Following acute HFD exposure, the regulation of food intake involves NMDARs-mediated currents, which occur in response to NMDARex activation. Understanding these events may provide a mechanistic basis for hyperphagia and identify potential novel therapeutic targets for the treatment of obesity.