It is known that bipolar disorder has a multifactorial aetiology where the interaction between genetic and environmental factors is responsible for its development. Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro‐amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14 days of dextro‐amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro‐amphetamine injections. Adult C57BL/6 mice received 7 days of valproate or sodium butyrate administration, being sleep deprived at the last 36 hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open‐field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro‐amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment.

中文翻译：

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表观遗传调节酶在苯丙胺和反常睡眠剥夺引起的躁狂症动物模型中的作用

众所周知，躁郁症具有多种病因，遗传和环境因素之间的相互作用是其发展的原因。因此，在精神疾病中对表观遗传学进行了大量研究。本研究旨在评估组蛋白脱乙酰基酶抑制剂对分别提交给右旋苯丙胺或睡眠剥夺引起的躁狂症动物模型的大鼠或小鼠表观遗传酶改变的影响。成年雄性Wistar大鼠要接受14天的右旋苯丙胺治疗，从第8天到第14天，除了注射右旋苯丙胺之外，还要用丙戊酸和丁酸钠治疗动物。成年C57BL / 6小鼠接受了7天的丙戊酸或丁酸钠的给药，在方案的最后36个小时被剥夺了睡眠。在野外试验中评估大鼠和小鼠的运动和探索活动，并评估额叶皮层，海马和纹状体中的组蛋白脱乙酰基酶，DNA甲基转移酶和组蛋白乙酰基转移酶活性。右旋苯丙胺和睡眠剥夺引起动物大脑活动亢进并增加组蛋白脱乙酰基酶和DNA甲基转移酶活性。丙戊酸和丁酸钠能够逆转这两种动物模型引起的运动过度，以及组蛋白脱乙酰酶和DNA甲基转移酶活性的改变。两种模型的酶活性和杂交次数之间呈正相关。组蛋白脱乙酰基酶和DNA甲基转移酶活性之间也呈正相关。