Connor T J, Kelly J P, Leonard B E
Department of Pharmacology, University College Galway, Ireland.
Pharmacol Biochem Behav. 1997 Dec;58(4):961-7. doi: 10.1016/s0091-3057(97)00028-2.
The forced swim test (FST) is a behavioral paradigm that is widely used as a screening test for antidepressant activity in rodents. The objectives of the present study were to characterize the corticosterone and immune responses and in addition to examine neurotransmitter levels, in five brain regions at intervals (15, 30, 60, 90, and 120 min) following the second exposure to the FST. There was a significant but transient reduction in noradrenaline and 5-HT concentrations, in the hypothalamus 15 min post-FST exposure. 5-HT turnover in the frontal cortex and amygdala was significantly increased between 20-120 min post-FST exposure. The FST elicited a robust corticosterone response that peaked significantly at 30 min and had almost returned to baseline 120 min after exposure. There was a significant reduction in total white blood cell count 120 min after the FST, which was accompanied by a significantly reduced percentage of lymphocytes 90 and 120 min post-FST exposure. In addition, there was a significant but transient suppression of both PHA and Con A-induced lymphocyte proliferation 15 min following FST exposure. This study demonstrates that there are neurochemical changes that are coincident with the endocrine and immune changes associated with FST exposure in rats. Furthermore, this model could be used to examine the effects of manipulation of this stress response by antidepressant drugs. Such an investigation could add to our understanding of the interactions between antidepressants, stress and the neuroendocrine and immune systems.
强迫游泳试验（FST）是一种行为范式，被广泛用作啮齿动物抗抑郁活性的筛选试验。本研究的目的是在第二次暴露于FST后的不同时间间隔（15、30、60、90和120分钟），对五个脑区的皮质酮和免疫反应进行表征，并检测神经递质水平。FST暴露后15分钟，下丘脑中去甲肾上腺素和5-羟色胺浓度显著但短暂降低。FST暴露后20 - 120分钟，额叶皮质和杏仁核中的5-羟色胺周转率显著增加。FST引发了强烈的皮质酮反应，在30分钟时达到峰值，暴露后120分钟几乎恢复到基线水平。FST后120分钟，白细胞总数显著减少，同时FST暴露后90和120分钟淋巴细胞百分比显著降低。此外，FST暴露后15分钟，PHA和Con A诱导的淋巴细胞增殖均受到显著但短暂的抑制。本研究表明，大鼠中存在与FST暴露相关的内分泌和免疫变化同时发生的神经化学变化。此外，该模型可用于研究抗抑郁药物对这种应激反应的影响。这样的研究可以增加我们对抗抑郁药、应激以及神经内分泌和免疫系统之间相互作用的理解。
