Escitalopram attenuates fear stress-induced increase in amygdalar dopamine following methamphetamine-induced sensitisation: Implications of fine-tuning action of selective serotonin reuptake inhibitors on emotional processing.
Escitalopram attenuates fear stress-induced increase in amygdalar dopamine following methamphetamine-induced sensitisation: Implications of fine-tuning action of selective serotonin reuptake inhibitors on emotional processing.
复制标题
艾司西酞普兰可减轻甲基苯丙胺引起的敏化后恐惧应激引起的杏仁核多巴胺的增加：选择性血清素再摄取抑制剂对情绪处理的微调作用的影响。
DOI：
10.1016/j.ejphar.2018.06.033
复制
发表时间：
2018
影响因子：
5
通讯作者：
Ken Inada a
中科院分区：
文献类型：
--
作者：
Hiroyuki Muraoka a;Hidehiro Oshibuchi a;Masahiko Kawano a;Takaaki Kawano a;Takahiro Tsutsumi a;Makiko Yamada a;Jun Ishigooka b;Katsuji Nishimura a;Ken Inada a
5-羟色胺再摄取抑制剂调节神经系统的多巴胺能通路，并广泛用于治疗精神疾病，如焦虑和抑郁。多巴胺能系统与这些疾病的发展有关。先前对甲基苯丙胺致敏大鼠（应激脆弱性的行为模型）的研究表明，杏仁核中的多巴胺释放增加，以应对条件应激。这种生化异常被认为是应激脆弱性的病理生理学基础。然而，5-羟色胺再摄取抑制剂对多巴胺水平的影响及其对情绪处理的影响尚不清楚。在这里，我们研究了艾司西酞普兰（一种高选择性5-羟色胺再摄取抑制剂）对模型大鼠杏仁核中恐惧相关行为、基线多巴胺释放和条件性恐惧应激反应中多巴胺释放的急性作用。雄性Sprague-Dawley大鼠接受2 mg/kg/天，s.c.的甲基苯丙胺10天，使他们对药物敏感，并建立了恐惧条件反射范式来模拟心理压力。应用微透析和高效液相色谱法测定了杏仁核对艾司西酞普兰全身给药后条件性恐惧应激反应的多巴胺变化。在非致敏大鼠中，艾司西酞普兰增加了杏仁核中的基线多巴胺释放，但在甲基苯丙胺致敏大鼠中没有。艾司西酞普兰减弱了致敏和非致敏大鼠对恐惧条件刺激的多巴胺释放。甲基苯丙胺致敏大鼠的抑制程度（-90%）大于非致敏大鼠（-48%）。这些研究结果表明，血清素再摄取抑制剂间接稳定多巴胺能通路和调节杏仁核的情绪处理。
Serotonin reuptake inhibitors modulate the serotonergic pathways of the nervous system and are widely used for treating psychiatric conditions such as anxiety and depression. The dopaminergic system is related to the development of these conditions. Previous studies on methamphetamine-sensitised rats (behavioural models of stress vulnerability) have shown increased release of dopamine in response to conditioned stress in the amygdala. This biochemical abnormality was proposed to underlie the pathophysiology of stress vulnerability. However, the effect of serotonin reuptake inhibitors on dopamine levels and its consequent impact on emotional processing is unclear. Here we examined the acute effect of escitalopram, a highly selective serotonin reuptake inhibitor, on fear-related behaviour, baseline dopamine release and dopamine release in response to conditioned fear stress in the amygdala of model rats. Male Sprague-Dawley rats received 2 mg/kg/day, s.c. of methamphetamine for 10 days to sensitise them to the drug, and a fear conditioning paradigm was instituted to model psychological stress. Dopamine changes in the amygdala in response to systemic administration of escitalopram followed by conditioned fear stress were measured using microdialysis and high-performance liquid chromatography. Baseline dopamine release in the amygdala was increased by escitalopram in non-sensitised rats but not in methamphetamine-sensitised rats. Escitalopram attenuated dopamine release in response to the fear-conditioned stimulus in both sensitised and non-sensitised rats. The extent of suppression in methamphetamine-sensitised rats (− 90%) was greater than that in non-sensitised rats (− 48%). These findings suggest that serotonin reuptake inhibitors indirectly stabilise the dopaminergic pathway and modulate emotional processing in the amygdala.