ANTIDEPRESSANT-LIKE BEHAVIORAL-EFFECTS OF SEROTONIN RECEPTOR AGONISTS
ANTIDEPRESSANT-LIKE BEHAVIORAL-EFFECTS OF SEROTONIN RECEPTOR AGONISTS
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DOI：
10.1016/0149-7634(94)90039-6
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发表时间：
1994-03-01
影响因子：
8.2
通讯作者：
KREISS, DS
中科院分区：
文献类型：
--
作者：
LUCKI, I;SINGH, A;KREISS, DS
临床发现，通过抑制5-羟色胺摄取或直接刺激突触后受体刺激5-羟色胺神经传递的药物具有抗抑郁特性，这激发了人们对确定5-羟色胺受体系统在抗抑郁药物临床效果中的作用的兴趣。本文综述了两种从动物行为学角度探讨抗抑郁药物治疗效果的神经化学中介作用的方法。第一种方法利用了大鼠的一种行为反应，即强迫游泳测试，这与预测人类服用抗抑郁药物有很好的相关性。本文综述了强迫游泳试验中5-羟色胺能化合物的研究，从确定更好的抗抑郁反应的5-羟色胺能机制的角度进行了综述。5-羟色胺摄取抑制剂和5-羟色胺受体激动剂在强迫游泳试验中产生的效果与其他类别的抗抑郁药物相似。相反，其他5-羟色胺受体激动剂或5-羟色胺受体拮抗剂不会产生类似于抗抑郁药的行为效应。5-HT1a受体拮抗剂阻止5-HT1a受体激动剂在强迫游泳试验中减少不动的能力的研究结果支持了5-HT1a受体在抗抑郁反应中发挥重要作用的证据。通过抑制5-羟色胺合成或破坏5-羟色胺神经元来干扰5-羟色胺神经传递的研究结果支持这样的观点，即5-HT1A受体激动剂的作用是通过刺激突触后的5-HT1A受体产生的。研究抗抑郁药物的行为效应的第二种方法是药物辨别研究，采用辨别性味觉厌恶程序，为研究抗抑郁剂5-羟色胺摄取抑制剂舍曲林的辨别性刺激效应提供了一种方法。训练大鼠辨别舍曲林(10 mg/kg)和生理盐水的作用。其他5-羟色胺摄取抑制剂，如氟西汀、氟伏沙明和帕罗西汀，可替代舍曲林刺激。需要大剂量的去甲肾上腺素摄取抑制剂，如地塞帕明或马普替林，才能产生类似的效果。这两种行为方法有望有助于确定与抗抑郁药物的行为效应相关的重要药理学效应。
The clinical discoveries that drugs that stimulate 5-HT neurotransmission, either by inhibiting 5-HT uptake or by stimulating postsynaptic receptors directly, have antidepressant properties has stimulated interest in defining the role of the 5-HT receptor system in the clinical effects of antidepressant drugs. Two approaches are reviewed in this paper that address the neurochemical mediation of the therapeutic effects of antidepressant drugs from the standpoint of animal behavior. The first approach utilizes a behavioral response in rats, the forced swimming test, that correlates well with predicting antidepressant drugs in humans. Studies are reviewed that examined serotonergic compounds in the forced swimming test, from the standpoint of identifying better serotonergic mechanisms involved in the antidepressant response. Both 5-HT uptake inhibitors and 5-HT1A receptor agonists produce effects in the forced swimming test that are similar to those of other classes of antidepressant drugs. In contrast, agonists at other 5-HT receptors or 5-HT receptor antagonists do not produce antidepressant-like behavioral effects. Evidence for an important role of 5-HT1A receptors in the antidepressant response is supported by findings that antagonists of 5-HT1A receptors prevent the ability of 5-HT1A receptor agonists to reduce immobility in the forced swimming test. The results of studies interfering with 5-HT neurotransmission, either by inhibition of 5-HT synthesis or by the destruction of 5-HT neurons, favor the idea that the effects of 5-HT1A receptor agonists are produced by the stimulation of postsynaptic 5-HT1A receptors. The second approach for studying the behavioral effects of antidepressant drugs employs drug discrimination studies, conducted using a discriminated taste aversion procedure, to provide a method for studying the discriminative stimulus effects of the antidepressant 5-HT uptake inhibitor sertraline. Rats were trained to discriminate the effects of sertraline (10 mg/kg) from saline. Other 5-HT uptake inhibitors, such as fluoxetine, fluvoxamine and paroxetine, substituted for the sertraline stimulus. High doses of norepinephrine uptake inhibitors, such as desipramine or maprotiline, were required to produce similar effects. These two behavioral approaches promise to be useful for defining the important pharmacological effects associated with the behavioral effects of antidepressant drugs.