Enhanced adrenergic excitation of serotonergic dorsal raphe neurons in genetically obese rats

Serotonergic neurons in the dorsal raphe nucleus (DRN) project to the ventromedial hypothalamus (VMH), where serotonin (5-HT) release modulates feeding. 5-HT release in the VMH is altered in genetically obese vs. lean Zucker rats. Serotonergic DRN neurons are subject to adrenergic and serotonergic neuromodulation. To determine if the difference in 5-HT release between lean and obese rats might be due to differences in these neuromodulatory pathways, we examined the effects of phenylephrine (PE) and 5-HT on serotonergic DRN neurons using current-clamp recording. Cells from lean and obese animals responded similarly to 5-HT, but cells from obese rats exhibited both a larger depolarization and increased firing rate in response to PE than did cells from lean rats. This indicates that DRN neurons of obese rats have an enhanced adrenergic drive.