Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Metabolism. 2012 Feb;61(2):229-36. doi: 10.1016/j.metabol.2011.06.013. Epub 2011 Aug 4.
Reports in humans advocate a link between hypoglycemia and altered mood. Such observations, however, have not been mechanistically explored. Here we examined depressive-like behaviors in mice resulting from acute hypoglycemia. Mice were fasted for 12 hours and then administered intraperitoneal insulin to induce a blood glucose nadir of 50 mg/dL at 0.75 hour after injection that by 2 hours postinjection had returned to normal. The behaviors of locomotion, forced swim, saccharin preference, and novel object recognition were subsequently examined. Mice made hypoglycemic showed depressive-like behaviors 24 hours after resolution of hypoglycemia as evidenced by increased immobility in the forced swim test (FST) and reduced saccharin preference. Movement and memory were not impacted by hypoglycemia 24 hours after its resolution. By 48 hours posthypoglycemia, depressive-like behaviors resolved. In contrast, neither peripheral insulin administration without resultant hypoglycemia nor intracerebroventricular insulin administration altered performance in the FST. The antidepressants fluoxetine and desipramine prevented hypoglycemia-induced immobility in the FST, as did the antiadrenergic agents phentolamine, metoprolol, and butoxamine. Epinephrine and norepinephrine administration caused increased immobility in the FST at 24 hours postadministration that subsequently resolved by 48 hours. These data indicate that, in mice, acute hypoglycemia through adrenergic pathways caused depressive-like behaviors that exist well beyond the resolution of hypoglycemia.
报告表明，低血糖与情绪改变之间存在关联。然而，这些观察结果尚未从机制上进行探讨。在这里，我们研究了急性低血糖导致的小鼠抑郁样行为。将小鼠禁食 12 小时，然后腹腔内注射胰岛素，以在注射后 0.75 小时使血糖降至 50mg/dL 的最低点，而在注射后 2 小时血糖已恢复正常。随后检查了运动、强迫游泳、蔗糖偏好和新物体识别的行为。低血糖缓解后 24 小时，低血糖小鼠表现出抑郁样行为，如强迫游泳试验（FST）中不动时间增加，蔗糖偏好降低。低血糖缓解后 24 小时，运动和记忆不受影响。低血糖后 48 小时，抑郁样行为得到缓解。相比之下，外周给予胰岛素而不引起低血糖或脑室给予胰岛素均未改变 FST 中的表现。抗抑郁药氟西汀和去甲替林可预防 FST 中由低血糖引起的不动，而肾上腺素能拮抗剂苯福林、美托洛尔和布他沙明也有此作用。肾上腺素和去甲肾上腺素在给药后 24 小时引起 FST 中不动时间增加，随后在 48 小时内恢复正常。这些数据表明，在小鼠中，通过肾上腺素能途径的急性低血糖导致了抑郁样行为，这种行为持续时间远远超过低血糖的缓解。
