El receptor nicotínico de acetilcolina en las neuronas orexinérgicas del hipotálamo lateral

A. P. GARCÍA

Jornada; 1er Jornada Científica: Los Mecanismos Neuronales que Controlan el Apetito.; 2018

Despite much data supporting a role for nicotine-mediated suppression of appetite, little is known about the mechanism of action of the endogenous neurotransmitter, acetylcholine (ACh), on this effect. To shed light on the hypothalamic circuits governing ACh regulation of appetite, we investigated the influence of (nAChRs) expressing the α4 subunit in rats. Immunocytochemical analysis revealed the expression of nAChR α4 subunit at different populations 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 hours 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 cFos, the immediate early gene marker for neuronal activity. No differential activity patterns where observed in the other populations of neurons analyzed. These results indicate that various neurochemically distinct hypothalamic circuits 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.