Swiergiel Artur H, Leskov Igor L, Dunn Adrian J
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Behav Brain Res. 2008 Jan 10;186(1):32-40. doi: 10.1016/j.bbr.2007.07.018. Epub 2007 Jul 20.
The effects of chronic footshock (CFS) on behavioral responses of CD1 mice to acute footshock and restraint were studied in tests commonly used to assess antidepressant treatments. Adult male mice were subjected to 20 min of footshock daily for 14-16 days, and then tested in the tail suspension test (TST) and the forced swim test (FST). CFS treatment did not alter immobility in the TST when mice were tested before the footshock on that day. However, when the TST was performed after the footshock, immobility decreased in both control and CFS mice. In the FST, chronic footshock significantly increased the time spent floating when mice were tested before footshock on that day. However, when the FST was performed immediately after the footshock, floating decreased in the CFS mice, but not in previously unshocked mice. Restraint, shortly before the FST, decreased floating in both CFS and unshocked mice. Thus, CFS induced depression-like activity in the FST, but not in the TST, whereas acute footshock or restraint immediately before testing induced antidepressant-like effects in both the TST and the FST. In unshocked mice, intracerebroventricular corticotropin-releasing factor (CRF) consistently decreased immobility in the TST and the FST, with significant effects at the 100ng dose. The same dose of CRF depressed activity in the open field, so that these changes in immobility are unlikely to reflect a change in overall activity. CRF thus mimicked the effects of the acute stressors in the TST and the FST. Responses to icv CRF were attenuated by chronic footshock suggesting that CFS desensitizes the brain to CRF. CFS treatment did not alter basal concentrations of ACTH and corticosterone in blood plasma. Acute footshock increased the plasma concentrations of the hormones but in CFS mice these responses were attenuated, significantly for plasma ACTH. Acute footshock activated brain dopamine, norepinephrine and serotonin metabolism, and increased tryptophan concentrations in the brain. In CFS mice, these responses were attenuated, significantly for hypothalamic NE.
在常用于评估抗抑郁治疗效果的实验中，研究了慢性足部电击（CFS）对CD1小鼠急性足部电击和束缚行为反应的影响。成年雄性小鼠每天接受20分钟的足部电击，持续14 - 16天，然后在悬尾实验（TST）和强迫游泳实验（FST）中进行测试。当在当天足部电击前对小鼠进行TST测试时，CFS处理并未改变小鼠的不动时间。然而，当在足部电击后进行TST时，对照组和CFS组小鼠的不动时间均减少。在FST中，当在当天足部电击前对小鼠进行测试时，慢性足部电击显著增加了小鼠漂浮的时间。然而，当在足部电击后立即进行FST时，CFS组小鼠的漂浮时间减少，而之前未受电击的小鼠则没有。在FST前不久进行束缚，会使CFS组和未受电击组小鼠的漂浮时间均减少。因此，CFS在FST中诱导出类似抑郁的行为，但在TST中未出现，而在测试前立即进行急性足部电击或束缚则在TST和FST中均诱导出类似抗抑郁的效果。在未受电击的小鼠中，脑室内注射促肾上腺皮质激素释放因子（CRF）持续减少TST和FST中的不动时间，在100 ng剂量时有显著效果。相同剂量的CRF降低了旷场实验中的活动，因此这些不动时间的变化不太可能反映整体活动的改变。因此，CRF在TST和FST中模拟了急性应激源的作用。慢性足部电击减弱了对脑室内注射CRF的反应，表明CFS使大脑对CRF脱敏。CFS处理并未改变血浆中促肾上腺皮质激素（ACTH）和皮质酮的基础浓度。急性足部电击增加了激素的血浆浓度，但在CFS小鼠中这些反应减弱，血浆ACTH的减弱尤为显著。急性足部电击激活了脑内多巴胺、去甲肾上腺素和5-羟色胺的代谢，并增加了脑内色氨酸的浓度。在CFS小鼠中，这些反应减弱，下丘脑去甲肾上腺素的减弱尤为显著。
