Mello Denise Maria de Sousa, Marcinichen Débora Ramos, Madruga Daniela, Branco Raphael, Paschoalini Marta Aparecida, De Lima Thereza Christina Monteiro
Department of Biological Sciences and Health, Universidade do Planalto Catarinense-UNIPLAC, Lages, Santa Catarina, Brazil.
Behav Brain Res. 2007 Aug 6;181(2):232-8. doi: 10.1016/j.bbr.2007.04.010. Epub 2007 Apr 24.
Substance P (SP) is involved in the pathophysiology of several psychiatric disorders and is considered a central stress neurotransmitter. Endogenous SP does not inhibit the initial extent of the HPA axis response to restraint stress, but reduces the duration of the stress suggesting that SP plays an important role in the transition between acute and chronic stress. Stress hormones can alter metabolic functions in white adipose tissue and liver. The HPA axis is the endocrine pathway that promotes lipolysis elevating free fatty acid levels (FFA) in blood, besides indirectly causing hyperglycemia. In the present study, changes in the blood levels of stress markers in the anxiogenic-like effects of SP, as evaluated on the elevated plus-maze (EPM), were studied in adult male rats. Serum corticosterone was used as the traditional stress marker, while the plasma FFA and glucose were used as alternative anxiety/stress markers. Our findings show: (a) elevated corticosterone levels, confirming the aversive situation induced by SP (behaviorally assessed in the EPM) and indicating SP as a "chemical" stressor; (b) elevated levels of FFA and glucose, indicators of stress-induced mobilization of energy substrates, confirming the stressor effect of SP; (c) FFA levels can be used as an accurate, sensitive and reliable index of acute stress situations, including in the anxiogenic-like effect of SP, with the FFA response being as good as corticosterone as a stress marker in this case; (d) NK1 receptors involvement in the underlying mechanisms of the behavioral and metabolic effects of SP. Finally, our study indicates that some of these physiological variables are positively related to the stressor intensity.
P物质（SP）参与多种精神疾病的病理生理过程，被认为是一种核心应激神经递质。内源性SP并不抑制下丘脑-垂体-肾上腺（HPA）轴对束缚应激的初始反应程度，但会缩短应激持续时间，这表明SP在急性应激和慢性应激的转变中起重要作用。应激激素可改变白色脂肪组织和肝脏的代谢功能。HPA轴是一种内分泌途径，除间接导致高血糖外，还能促进脂肪分解，提高血液中游离脂肪酸水平（FFA）。在本研究中，我们在成年雄性大鼠身上研究了，通过高架十字迷宫（EPM）评估的，SP致焦虑样效应中应激标志物血液水平的变化。血清皮质酮被用作传统应激标志物，而血浆FFA和葡萄糖被用作替代性焦虑/应激标志物。我们的研究结果表明：（a）皮质酮水平升高，证实了SP诱导的厌恶情境（在EPM中进行行为评估），并表明SP是一种“化学”应激源；（b）FFA和葡萄糖水平升高，这是应激诱导能量底物动员的指标，证实了SP的应激源效应；（c）FFA水平可作为急性应激情况的准确,敏感和可靠指标，包括在SP的致焦虑样效应中，在这种情况下，FFA反应作为应激标志物与皮质酮一样好；（d）NK1受体参与了SP行为和代谢效应的潜在机制。最后，我们的研究表明，其中一些生理变量与应激源强度呈正相关。
