Balk Rodrigo de Souza, Silva Michele Hinerasky da, Bridi Jessika Cristina, Carvalho Nelson Rodrigues, Portella Rafael de Lima, Dobrachinski Fernando, Amaral Guilherme Pires, Barcelos Rômulo, Dias Glaecir Roseni Mundstock, Rocha João Batista Teixeira da, Barbosa Nilda Berenice Vargas, Soares Felix Alexandre Antunes
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, Brazil.
Int J Dev Neurosci. 2011 Dec;29(8):909-16. doi: 10.1016/j.ijdevneu.2011.06.010. Epub 2011 Jul 6.
Activation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) and the release of glucocorticoids are fundamental for the adaptive response and immediate survival of an organism in reaction to acute stimuli. However, high levels of glucocorticoids in the brain may produce neuronal injury and a decrease of Na(+)/K(+)-ATPase activity, with effects on neurotransmitter signaling, neural activity, as well as the whole animal behavior. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and LHPA axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. The purpose of the present study was to compare the effect of repeated restraint stress and clomipramine treatment on Na(+)/K(+)-ATPase activity and on the behavior of male rats. Changes in the behavioral response were evaluated by measuring the memory, learning, anxiety, and exploratory responses. Our results showed that exposure to repeated restraint stress reduced levels of Na(+)/K(+)-ATPase in brain structures and changed short and long-term memory, learning, and exploratory response when compared to the control group. Exposure to clomipramine treatment increased anxiety levels and reduced Na(+)/K(+)-ATPase activity in the cerebral cortex as well as short term memory, learning, and exploratory response. In conclusion, the present results provide additional evidence concerning how repeated restraint stress and clomipramine chronically administered at higher dose levels affect the neural activity and behavior of male rats.
边缘系统-下丘脑-垂体-肾上腺轴（LHPA）的激活以及糖皮质激素的释放，对于生物体在应对急性刺激时的适应性反应和即时生存至关重要。然而，大脑中高水平的糖皮质激素可能会导致神经元损伤以及钠钾ATP酶活性降低，从而影响神经递质信号传导、神经活动以及动物的整体行为。氯米帕明是一种三环类抗抑郁药，它通过对多巴胺能系统和LHPA轴的间接作用来抑制血清素和去甲肾上腺素的再摄取。长期使用氯米帕明可增强机体应对压力的能力；然而，高剂量使用会增强其对记忆、学习和感觉运动功能的副作用。本研究的目的是比较重复束缚应激和氯米帕明治疗对雄性大鼠钠钾ATP酶活性及行为的影响。通过测量记忆、学习、焦虑和探索反应来评估行为反应的变化。我们的结果表明，与对照组相比，重复束缚应激会降低脑结构中钠钾ATP酶的水平，并改变短期和长期记忆、学习及探索反应。氯米帕明治疗会增加焦虑水平，降低大脑皮质中的钠钾ATP酶活性以及短期记忆、学习和探索反应。总之，本研究结果为重复束缚应激和高剂量长期使用氯米帕明如何影响雄性大鼠的神经活动和行为提供了更多证据。
