Duchesne Annie, Dufresne Marc M, Sullivan Ron M
Centre de Recherche Fernand-Seguin, Département de Psychiatrie, Université de Montréal, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):251-61. doi: 10.1016/j.pnpbp.2008.11.012. Epub 2008 Dec 3.
Stress-related psychopathology is particularly prevalent in women, although the neurobiological reason(s) for this are unclear. Dopamine (DA) and serotonin (5-HT) systems however, are known to play important adaptive roles in stress and emotion regulation. The aims of the present study included examination of sex differences in stress-related behaviour and neuroendocrine function as well as post mortem neurochemistry, with the main hypothesis that corticolimbic DA and 5-HT systems would show greater functional activity in males than females. Long-Evans rats of both sexes were employed. Additional factors incorporated included differential postnatal experience (handled vs. nonhandled) and adult mild stress experience (acute vs. repeated (5) restraint). Regional neurochemistry measures were conducted separately for left and right hemispheres. Behaviourally, females showed more exploratory behaviour than males in the elevated plus maze and an openfield/holeboard apparatus. Females also exhibited significantly higher levels of adrenocorticotrophic hormone and corticosterone at all time points in response to restraint stress than males across treatment conditions, although both sexes showed similar habituation in stress-induced ACTH activation with repeated mild stress. Neurochemically, females had significantly higher levels of DA (in ventromedial prefrontal cortex (vmPFC), insular cortex and n. accumbens) and 5-HT (in vmPFC, amygdala, dorsal hippocampus and insula) than males. In contrast, males had higher levels of the DA metabolite DOPAC or DOPAC/DA ratios than females in all five regions and higher levels of the 5-HT metabolite 5-HIAA or 5-HIAA/5-HT ratios in vmPFC, amygdala and insula, suggesting greater neurotransmitter utilization in males. Moreover, handling treatment induced a significant male-specific upregulation of 5-HT metabolism in all regions except n. accumbens. Given the adaptive role of 5-HT and DAergic neurotransmission in stress and emotion regulation, the intrinsic sex differences we report in the functional status of these systems across conditions, may be highly relevant to the differential vulnerability to disorders of stress and emotion regulation.
与压力相关的精神病理学在女性中尤为普遍，尽管其神经生物学原因尚不清楚。然而，已知多巴胺（DA）和血清素（5-HT）系统在压力和情绪调节中发挥重要的适应性作用。本研究的目的包括检查与压力相关行为和神经内分泌功能以及死后神经化学方面的性别差异，主要假设是皮质边缘DA和5-HT系统在雄性中比雌性表现出更大的功能活性。使用了两性的Long-Evans大鼠。纳入的其他因素包括不同的产后经历（处理过与未处理过）和成年期轻度压力经历（急性与反复（5次）约束）。分别对左右半球进行区域神经化学测量。行为方面，在高架十字迷宫和旷场/洞板装置中，雌性比雄性表现出更多的探索行为。在所有处理条件下，雌性在应对约束压力的所有时间点也表现出比雄性显著更高水平的促肾上腺皮质激素和皮质酮，尽管两性在反复轻度压力引起的应激诱导促肾上腺皮质激素激活方面表现出相似的习惯化。神经化学方面，雌性在腹内侧前额叶皮质（vmPFC）、岛叶皮质和伏隔核中的DA水平以及在vmPFC、杏仁核、背侧海马体和岛叶中的5-HT水平显著高于雄性。相反，在所有五个区域中，雄性的DA代谢物DOPAC或DOPAC/DA比率高于雌性，在vmPFC、杏仁核和岛叶中，雄性的5-HT代谢物5-HIAA或5-HIAA/5-HT比率更高，这表明雄性中神经递质的利用率更高。此外，除伏隔核外，处理过的大鼠在所有区域均诱导了5-HT代谢的显著雄性特异性上调。鉴于5-HT和多巴胺能神经传递在压力和情绪调节中的适应性作用，我们报告的这些系统在不同条件下功能状态的内在性别差异，可能与压力和情绪调节障碍的易感性差异高度相关。
