The mechanisms that mediate intentional self-starvation in individuals with anorexia nervosa are unknown. Kucukdereli et al. now show that female mice with high levels of baseline anxiety actively seek out a starvation-like state when exposed to stress.

In rodents, food restriction and the activation of fasting-sensitive agouti-related peptide (AgRP)-expressing hypothalamic neurons can be anxiolytic, prompting Kucukdereli et al. to consider whether animals might undertake self-starvation to mitigate the anxiogenic effects of stress. To examine this, they developed a virtual-reality protocol in which mice chose whether to spend time in a location associated with optogenetic stimulation of AgRP neurons (mimicking a starvation-like state) or a neutral location. In the absence of stress, most male mice avoided AgRP neuron stimulation, but only a subset of female mice showed such an aversion.