Nicotinic α4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits

A. P. GARCÍA; TEEMU AITTA-AHO; LAURA SCHAAF; NICHOLAS HEELEY; LENA HEUSCHMID; YUNJING BAI; FRANCISCO J BARRANTES; JOHN APERGIS-SCHOUTE

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Despite much data supporting a role on nicotine-mediated suppression of appetite, the mechanism by which acetylcholine?s (ACh), the endogenous nicotinic receptor agonist acts, has received little attention. To shed light on the hypothalamic circuits governing ACh regulation of appetite, we investigated the influence of nicotinic acetylcholine receptors (nAChRs) expressing the α4 subunit in rats. Immunocytochemical analysis revealed the expression of nAChR α4 subunit at different population of hypothalamic neurons (orexin/hypocretin (HO), melanin concentrating hormone (MCH), oxytocin, and tyrosine hydroxylase (TH)-containing neurons). We found that antagonizing the α4β2 nAChR locally in the lateral hypothalamus with DHβE, an α4 nAChR antagonist with moderate affinity, caused an increase in food intake after a 12 h fast, compared to saline-infused rats. Systemic DHβE (2 mg/kg) administration similarly increased food intake. In these animals a subpopulation of OH neurons showed elevated activity compared to controls and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. No differential activity patterns where observed in the other population of neurons analyzed. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of α4β2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local α4β2 nAChR-mediated transmission.