Hepato-vagal pathway associated with nicotineʹs anorectic effect in the rat

Nicotine reduces appetite and body weight. Because the hepato-portal area senses different types of nutrients that transmit signals via vagal afferent nerves to the hypothalamus to modify food intake and feeding pattern, we investigated the effect of nicotine on a hepato-vagal–hypothalamic pathway. Low doses of nicotine (<10 ng) injected into portal vein (ipv) decreased, while high doses of nicotine increased (≥10 ng) electrophysiological activity of hepatic vagal afferents. Stimulatory effect of high dose of nicotine on vagal hepatic afferents was blocked by a prior ipv injection of curare (30 μg) or hexamethonium (1 mg). Furthermore, activities of gastric vagal and adrenal sympathetic efferents were suppressed by low-dose, but stimulated by high-dose ipv nicotine. These reflex effects did not occur in hepatic vagotomized rats. Results of experiments demonstrate that in addition to nicotineʹs anorectic effect being mediated via a direct central action, nicotine also acts peripherally via hepatic vagal afferents from sensors of nicotine in the hepato-portal region.