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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Evidence for a role of inhibition of orexinergic neurons in the anxiolytic and sedative effects of diazepam: A c-Fos study
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Evidence for a role of inhibition of orexinergic neurons in the anxiolytic and sedative effects of diazepam: A c-Fos study

机译：c-Fos研究表明，抑制食欲能神经元在地西epa的抗焦虑和镇静作用中起作用的证据

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The classical benzodiazepine diazepam (DZ) induces anxiolysis at low doses and sedation and hypnosis at higher doses. Different brain areas and neuronal populations most likely mediate these different behavioral effects. We used c-Fos immunohistochemistry as an indirect way to study neuronal activation or inhibition induced by DZ at anxiolytic and sedative doses (0.5 and 5 mg/kg, respectively) in various brain areas involved in anxiety, arousal, sedation and addiction in C57BL/6J mice. We also focused on the two neuronal populations, orexinergic and dopaminergic neuronal populations, with the help of double-immunohistochemistry using c-Fos and orexin-A antibodies and c-Fos and tyrosine hydroxylase antibodies. We found that different brain areas of unhabituated mice reacted differently to the mild stress induced by vehicle injection. Also the response to anxiolytic or sedative doses of DZ differed between the areas, suggesting that distinct brain areas mediate the behavioral effects of low and high DZ doses. Our findings propose a role for inhibition of orexin neurons in the anxiolytic and sleep-promoting effects of DZ. In addition, the activation of central amygdala neurons by DZ treatment was associated with anxiolytic and sedative effects. On the other hand, the ventral hippocampus, basolateral amygdala, ventral tegmental area and prefrontal cortex were sensitive even to the mild injection stress, but not to the anxiolytic dose of DZ.
机译：经典的苯二氮卓地西epa（DZ）在低剂量时会引起抗焦虑作用，在高剂量时会引起镇静和催眠作用。不同的大脑区域和神经元种群最有可能介导这些不同的行为影响。我们使用c-Fos免疫组织化学作为间接方法来研究在涉及C57BL /的焦虑，唤醒，镇静和成瘾的各个大脑区域中，DZ在抗焦虑和镇静剂量（分别为0.5和5 mg / kg）下诱导的神经元激活或抑制。 6J小鼠。在使用c-Fos和orexin-A抗体以及c-Fos和酪氨酸羟化酶抗体的双重免疫组化的帮助下，我们还关注了两个神经元群体，即orexinergic和多巴胺能神经元群体。我们发现，不习惯的小鼠的不同大脑区域对由媒介物注射引起的轻度压力的反应不同。区域之间对DZ的抗焦虑或镇静剂量的反应也不同，这表明不同的大脑区域介导了低剂量和高剂量DZ的行为影响。我们的发现提出了在DZ的抗焦虑和促睡眠作用中抑制食欲素神经元的作用。此外，通过DZ处理激活中央杏仁核神经元与抗焦虑和镇静作用有关。另一方面，腹侧海马，基底外侧杏仁核，腹侧被盖区和前额叶皮层对轻度注射压力敏感，但对DZ的抗焦虑剂量不敏感。

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