Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.
Antidepressant-like effect of tetrahydroisoquinoline amines in the animal model of depressive disorder induced by repeated administration of a low dose of reserpine: behavioral and neurochemical studies in the rat.
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DOI：
10.1007/s12640-013-9454-8
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发表时间：
2014-07
影响因子：
3.7
通讯作者：
Michaluk J
中科院分区：
文献类型：
--
作者：
Antkiewicz-Michaluk L;Wąsik A;Możdżeń E;Romańska I;Michaluk J
动物模型被广泛用于研究啮齿类动物的抗抑郁药样作用。然而，应该指出的是，药理学模型并不总是考虑到疾病过程的复杂性。在本文中，我们证明了小剂量利血平(0.2 mg/kg i.p.)反复但非急性治疗。导致了一种抑郁症的药理模型，该模型基于其对囊泡单胺转运体2的抑制作用和大脑中单胺的耗竭作用。事实上，我们观察到，低剂量利血平慢性治疗在强迫游泳试验(FST)中诱导了明显的抑郁样行为，此外，它还显著降低了脑结构中多巴胺、去甲肾上腺素和5-羟色胺的水平。1，2，3，4-四氢异喹啉(TIQ)及其紧密的甲基衍生物1-甲基-1，2，3，4-四氢异喹啉(1MeTIQ)是哺乳动物大脑中自然存在的外源/内源性胺，在FST和利血平抑郁模型中显示出显著的抗抑郁药样作用。这两种化合物都是TIQ和1MeTIQ，长期给药，剂量为25 mg/kg(Ip)。利血平与利血平一起完全拮抗利血平所致的抑郁，通过不动时间和游泳时间来评估。生化数据与行为实验一致，表明与急性给药相比，长期服用小剂量利血平会显著抑制脑结构中的单胺类物质，并损害它们的新陈代谢。这些神经化学效应是由利血平(0.2 mg/kg ip)反复给药引起的。联合TIQ或1MeTIQ(25 mg/kg，i.p)可完全拮抗大鼠脑内各结构的损伤。服用慢性利血平。讨论了TIQ和1MeTIQ抗抑郁作用的可能分子机制。在现有的行为学和生化研究的基础上，我们认为这两种化合物作为新的抗抑郁药物在临床上可能是有效的，因为它们在外周给药时容易穿透血脑屏障，而且作为内源性化合物可能没有不良反应。
Animal models are widely used to study antidepressant-like effect in rodents. However, it should be mentioned that pharmacological models do not always take into account the complexity of the disease process. In the present paper, we demonstrated that repeated but not acute treatment with a low dose of reserpine (0.2 mg/kg i.p.) led to a pharmacological model of depression which was based on its inhibitory effect on the vesicular monoamine transporter 2, and monoamines depleting action in the brain. In fact, we observed that chronic treatment with a low dose of reserpine induced a distinct depressive-like behavior in the forced swim test (FST), and additionally, it produced a significant decrease in the level of dopamine, noradrenaline, and serotonin in the brain structures. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its close methyl derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) are exo/endogenous amines present naturally in the mammalian brain which demonstrated a significant antidepressant-like effect in the FST and the reserpine model of depression in the rat. Both compounds, TIQ and 1MeTIQ, administered chronically in a dose of 25 mg/kg (i.p.) together with reserpine completely antagonized reserpine-produced depression as assessed by the immobility time and swimming time. Biochemical data were in agreement with behavioral experiments and demonstrated that chronic treatment with a low dose of reserpine in contrast to acute administration produced a significant depression of monoamines in the brain structures and impaired their metabolism. These neurochemical effects obtained after repeated reserpine (0.2 mg/kg i.p.) in the brain structures were completely antagonized by joint TIQ or 1MeTIQ (25 mg/kg i.p.) administration with chronic reserpine. A possible molecular mechanism of action of TIQ and 1MeTIQ responsible for their antidepressant action is discussed. On the basis of the presented behavioral and biochemical studies, we suggest that both compounds may be effective for the therapy of depression in clinic as new antidepressants which, when administered peripherally easily penetrate the blood–brain barrier, and as endogenous compounds may not have adverse side effects.
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影响因子：
3.7
作者：
Antkiewicz-Michaluk L;Wąsik A;Michaluk J
通讯作者：
Michaluk J
影响因子：
64.5
作者：
LIU, YJ;PETER, D;EDWARDS, RH
通讯作者：
EDWARDS, RH
影响因子：
5.8
作者：
GRUNEWALD, GL;REITZ, TJ;RUTLEDGE, CO
通讯作者：
RUTLEDGE, CO
影响因子：
3.4
作者：
Cryan, JF;Page, ME;Lucki, I
通讯作者：
Lucki, I
影响因子：
4.7
作者：
Antkiewicz-Michaluk, L;Michaluk, J;Vetulani, J
通讯作者：
Vetulani, J