Assessing the effects of stress on feeding behaviors in laboratory mice

Abstract

Stress often affects eating behaviors, increasing caloric intake in some individuals and decreasing it in others. The determinants of feeding responses to stress are unknown, in part because this issue is rarely studied in rodents. We focused our efforts on the novelty-suppressed feeding (NSF) assay, which uses latency to eat as readout of anxiety-like behavior, but rarely assesses feeding per se. We explored how key variables in experimental paradigms – estrous and diurnal cyclicity, age and duration of social isolation, prandial state, diet palatability, and elevated body weight – influence stress-induced anxiety-like behavior and food intake in male and female C57BL/6J mice. Latency to eat in the novel environment is increased in both sexes across most of the conditions tested, while effects on caloric intake are variable. In the common NSF assay (i.e., lean mice in the light cycle), sex-specific effects of the length of social isolation, and not estrous cyclicity, are the main source of variability. Under conditions that are more physiologically relevant for humans (i.e., overweight mice in the active phase), the novel stress now elicits robust hyperphagia in both sexes . This novel model of stress eating can be used to identify underlying neuroendocrine and neuronal substrates. Moreover, these studies can serve as a framework to integrate cross-disciplinary studies of anxiety and feeding related behaviors in rodents.

High fat diet blunts stress-induced hypophagia and activation of Glp1r dorsal lateral septum neurons in male but not in female mice

“…In agreement with our findings, a recent study used novelty-suppressed feeding (NSF) to show that latency to consume food was equally increased in male and female mice, but while novel environment stress reduced food intake in male mice, it had no effect on food intake in female mice [ 17 ]. Furthermore, when rendered obese, both male and female mice displayed hyperphagia in response to novel environment stress [ 17 ]. Interestingly, another study showed the opposite effect, with female, but not male, mice displaying reduced food intake during a novelty-suppressed feeding test [ 66 ].…”

“…Sex can affect various responses to stress in rodents [ 20 , 23 , 29 , 37 , 56 ], including effects on feeding behavior [ [46] , [67] ]. The directionality of the effect and whether there is even a sex-dependent response to stress depends on the type, duration, and/or intensity of the stressor as well as other factors such as age of the mice and time of day in which the stressor is executed [ 17 ]. In agreement with our findings, a recent study used novelty-suppressed feeding (NSF) to show that latency to consume food was equally increased in male and female mice, but while novel environment stress reduced food intake in male mice, it had no effect on food intake in female mice [ 17 ].…”

“…Interestingly, another study showed the opposite effect, with female, but not male, mice displaying reduced food intake during a novelty-suppressed feeding test [ 66 ]. These discrepant findings are likely due to differences in which the NSF protocols were conducted [ 17 , 66 ]. Nevertheless, our observation that there was no difference in dLS Glp1r neuronal activity during stress between lean and obese female mice further supports the proposed role for dLS Glp1r neurons in the regulation of post-stress feeding.…”

Identification of a stress-sensitive anorexigenic neurocircuit from medial prefrontal cortex to lateral hypothalamus

“…To examine the role of acute stress on motivated reward seeking, we conducted a progressive ratio experiment in a novel environment, a validated model of acute stress that affects feeding (29). Following CNO injections, we observed that active nose pokes were suppressed during the first 5 minutes compared to the home cage (Fig 3M), confirming that acute stress transiently affects motivated reward seeking.…”

“…To examine the role of acute stress on motivated reward seeking, we conducted a progressive ratio experiment in a novel environment, a validated model of acute stress that affects feeding (29).Following CNO injections, we observed that active nose pokes were suppressed during the first 5 minutes compared to the home cage ( Interestingly, rearing behavior is typically expressed within a novel environment to survey for potential danger or threat (30). Collectively, these results suggest that mPFC-LH inhibition alleviates the stress-induced decrease in motivation for sucrose pellets and the avoidance of novel food or food presented in a novel environment.…”