Kudryashov N V, Kalinina T S, Shimshirt A A, Volkova A V, Narkevich V B, Naplekova P L, Kasabov K A, Kudrin V S, Voronina T A, Fisenko V P
Federal State Budgetary Institution «Research Zakusov Institute of Pharmacology», Moscow, 125315 Russia.
Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991 Russia.
Acta Naturae. 2020 Jan-Mar;12(1):63-72. doi: 10.32607/actanaturae.10942.
The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant- like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress.
研究了在远交群ICR（CD-1）小鼠不可预测的轻度应激环境下单次和长期给予阿米替林（10毫克/千克，腹腔注射）和氟西汀（20毫克/千克，腹腔注射）后的行为和神经化学效应。在应激暴露28天后，我们观察到小鼠在强迫游泳试验中的抑郁反应增加，海马中血清素（5-羟色胺，5-HT）和5-羟吲哚乙酸（5-HIAA）水平降低，而下丘脑去甲肾上腺素（NA）水平升高。单次和长期给予阿米替林和氟西汀可缩短强迫游泳试验中的不动时间，并增加主动游泳时间。单次注射后，氟西汀而非阿米替林的抗抑郁样效应与海马中5-HT周转率增加一致。长期给予抗抑郁药可增加下丘脑NA水平。因此，阿米替林和氟西汀的抗抑郁样效应可能是由于增强了被慢性应激耗尽的应激依赖性适应性机制。
