Defining the Role of Locus Coeruleus Noradrenergic Neurons in the Modulation of Homeostatic Feeding

The locus coeruleus (LC) is a hindbrain structure that is the major source of norepinephrine (NE) input to the cortex and other forebrain areas. It is involved in processes of arousal, attention, and stress. It has been shown that the locus coeruleus norepinephrine system is also involved in the modulation of feeding. In this experiment, we used triple transgenic mice expressing the hM3Dq receptor in LC-NE neurons. These mice and littermate controls were overnight fasted then injected with vehicle or deschloroclozapine (DCZ), which is an inert ligand that solely activates the designer hM3Dq receptor. The mice were then immediately placed in a feeding assay, where their food intake was measured at set time points over three hours. We found that activation of LC-NE neurons via administration of DCZ to the triple transgenic mice suppressed feeding compared to those injected with vehicle, especially at 3-hours post-injection. Additionally, we found that LC activation suppressed feeding in female mice more than in male mice. The results suggest that this dose of DCZ is effective at inducing a change in behavior in mice. The data also supports the idea that the LC-NE system is involved in the modulation of homeostatic feeding