Acute hypoglycemia causes extended anhedonia in mice

Abstract

In humans, hypoglycemia is associated with a variety of mood changes including a reduction in hedonic tone and energetic arousal and an increase in tense arousal. While these clinical symptoms are well characterized, their underlying mechanism is not. C57BL/6J mice were administered insulin that generated a blood glucose nadir of 56 ± 6 mg/dl 0.75 h after injection. At 4 h post insulin administration blood glucose had returned to normal (151 ± 19 mg/dl). Saccharin preference testing 24 h post hypoglycemia showed that insulin receiving mice had saccharin aversion (30 % vs 81 % of total fluid consumption) that took 72 h to resolve. In addition, insulin administered mice (24 h post hypoglycemia) had decreased mobility in the forced swim test and the tail suspension test that took 48 h to rectify. Importantly, activity and burrowing were not impacted 24 h post hypoglycemia. Taken together these data indicate that anhedonia and depressive‐like behavior are induced by hypoglycemia and resolve much more slowly than hypoglycemia, itself, or behaviors associated with locomotion and tunnel maintenance.This research was supported by grants from National Institutes of Health (DK64862 and NS58525 to G.G.F.) and University of Illinois Agricultural Experiment Station (to G.G.F.).