Involvement of Cholinergic Pathway in Energy Homeostasis via Ventromedial Hypothalamic D2 Receptors

  Studies indicate that dopamine, particularly via D2 receptors (D2R), has an important role in energy homeostasis. Our previous study demonstrated that hypothalamic D2Rs, through dorsal vagus complex, are involved in the regulation of ghrelin secretion. In present study, we evaluated whether vagus cholinergic system could play a role in the regulation of leptin and glucose plasma levels by hypothalamic ventromedial nucleus (VMH) D2Rs? Canulation was performed into the VMH in Wistar rats (220-250 g). In experiment day, fasted rats (for 20-24 hours) received atropine (cholinergic antagonist, 5 mg⁄ kg subcutaneously) or saline. Thirty minutes later, D2R agonist (Quinpilroe, 0.5 µg) or antagonist (Sulpiride, 0.005 µg) and saline (0.5 µl) were injected into the VMH. Then, blood samples were collected 0, 30, and 60 minutes later, and plasma leptin and glucose levels were measured using enzyme-linked immunosorbent assay (ELISA) kit and glucose oxidase method, respectively. Plasma leptin significantly decreased in a time-dependent manner in atropine-Quinpirole group compared to control group (P < 0.001); while increase in glucose levels was time-dependently stable in atropine-Quinpirole group (P < 0.001). No significant change was observed in leptin levels in atropine-Sulpiride group compared to control group. VMHD2Rs exert their effects on the regulation of leptin and glucose levels, at least partly, via vagus cholinergic pathway.