Fig 6. Chemogenetic silencing of LH GABAergic neurons potentiates tesofensine’s anorexigenic effects.

A. Representative image of LH in mouse expressing hM4D(Gi), which inhibits GABAergic neurons chemogenetically. B. Schematic of a task where mice were placed in their home cages with an automated feeder (FED3) that delivered chocolate pellets for each nose poke. Recording started at 18:00 and lasted for 24 hours. At 18:30 h, the same five mice were injected with vehicle (Veh), Clozapine-N-Oxide (CNO), a ligand for hM4D(Gi), tesofensine (2 mg/kg), and CNO + tesofensine. The dark cycle lasted from 19:00 to 7:00 h. The moon symbol indicates when the ambient lights were turned off and the sun when the lights were turned on. C. Average cumulative nose pokes during the 24-hour recordings for each group. The syringe indicates the time of drug administration at 18:30. The teso+CNO group performed fewer cumulative nose pokes and thus obtained fewer pellets than the other groups. * Significantly different two-sample Kolmogorov-Smirnov test (for the first 19 hours after drug administration, see horizontal line); Veh vs. CNO p = 0.006, CNO vs. Teso; p = 0.01, and Teso vs. Teso+CNO p = 0.04.