Ghrelin, a gastric peptide hormone, has been reported to regulate growth hormone secretion and energy homeostasis. Here we show that ghrelin promotes neural proliferation in vivo and in vitro in the rat dorsal motor nucleus of the vagus (DMNV). Ghrelin receptor mRNA and immunoreactivity were detected in tissues from DMNV. Systemic administration of ghrelin (130 nmol/kg) significantly increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in the DMNV in adult rats with cervical vagotomy from 27±4 to 69±14 (n=5, P<0.05). In vitro, exposure of cultured DMNV neurons to ghrelin significantly increased the percentage of BrdU incorporation into cells in both dose-dependent (10^-9 to 10^-6M), and time-dependent (6 hrs to 48 hrs) manners. Ghrelin significantly increased voltage-activated calcium currents in isolated single DMNV neurons from a mean maximal change of 141±26 pA to 227±37 pA. Upon removal of ghrelin, calcium currents slowly returned to baseline. Blocking L-type calcium channels by diltiazem (10 µM) significantly attenuated ghrelin-mediated increments in BrdU incorporation (n=5, P<0.05). Ghrelin acts directly on DMNV neurons to stimulate neurogenesis