Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA, USA.
Department of Kinesiology, Iowa State University, Ames, IA, USA.
J Nutr. 2021 Dec 3;151(12):3617-3627. doi: 10.1093/jn/nxab298.
Adverse life experiences are a major risk factor for anorexia nervosa (AN). Eating-provoked anxiousness associated with AN is postulated to be due to food-related exaggerated serotonin activity in the brain and imbalances of monoamine neurotransmitters.
Using a rodent model of stress-induced hypophagia, we investigated if stress exposure augments food-related serotonin turnover and imbalances in measures of brain serotonin and dopamine activity in manners consistent with anxiousness toward food and restricted eating.
Adult male F344 rats were conditioned to associate an audio cue with daily food over 2 weeks, after which half of the rats were exposed to a single episode of tail shocks (stress) or left undisturbed (nonstressed). All rats were killed 48 h later, during a control period, the food-associated cue, or a period of food access. Serotonin, dopamine, and norepinephrine, as well as metabolite concentrations, were assessed across brain regions comprising reward, emotion, and feeding circuits relevant to AN in acutely stressed and nonstressed rats using HPLC. Statistical significance level was 5%.
Stress-induced rat hypophagia paralleled an augmented serotonin turnover in response to the food-associated cue in the hypothalamus and hippocampus, as well as food access in the hypothalamus and cortical areas (all P < 0.05). Stress exposure increased the ratio of serotonin to dopamine metabolites across several brain areas, but the magnitude of this imbalance was further augmented during the food-associated cue and food access in the brainstem, hippocampus, and cortical areas (all P < 0.05). Finally, stress lowered norepinephrine concentrations by 18% in the hypothalamus (P < 0.05).
The observed stress-induced changes to monoamine profiles in rats could have key implications for physiological states that contribute to restricted eating and may hold relevance for the development of AN precipitated by adverse life experiences.
不良生活经历是厌食症（AN）的一个主要风险因素。与 AN 相关的进食引起的焦虑被认为是由于大脑中与食物相关的 5-羟色胺活动过度和单胺神经递质失衡所致。
我们使用应激诱导摄食减少的啮齿动物模型，研究应激暴露是否会以与食物相关的焦虑和限制进食相一致的方式增强与食物相关的 5-羟色胺周转率以及大脑 5-羟色胺和多巴胺活性的失衡。
成年雄性 F344 大鼠在 2 周内接受音频提示与每日食物的关联条件作用，之后一半大鼠接受单次尾部电击（应激）或不受干扰（非应激）。所有大鼠在 48 小时后处死，在此期间进行对照期、食物相关提示期或进食期。使用 HPLC 评估与 AN 相关的奖赏、情绪和摄食回路的脑区中涉及的 5-羟色胺、多巴胺和去甲肾上腺素以及代谢物浓度。统计学显著性水平为 5%。
应激诱导的大鼠摄食减少与下丘脑和海马中对食物相关提示的 5-羟色胺周转率增加以及下丘脑和皮质区的进食增加平行（均 P < 0.05）。应激暴露增加了几个脑区中 5-羟色胺与多巴胺代谢物的比值，但在脑桥、海马和皮质区的食物相关提示和进食期间，这种失衡的幅度进一步增加（均 P < 0.05）。最后，应激使下丘脑的去甲肾上腺素浓度降低了 18%（P < 0.05）。
在大鼠中观察到的应激诱导的单胺谱变化可能对导致限制进食的生理状态具有重要意义，并且可能与不良生活经历引发的 AN 发展有关。
