抗抑郁剂慢性给药对强迫游泳大鼠下丘脑c-Fos蛋白表达水平的下调作用

Chronic treatment of antidepressants downregulates cFos protein expression in hypothalamus of forcedswimming rats

应用ｃ－Ｆｏｓ蛋白免疫组织化学定位观察的方法，在强迫游泳大鼠抑郁模型上，观察地昔帕明（５，２０ｍｇ·ｋｇ－１），吗氯贝胺（１０，４０ｍｇ·ｋｇ－１）和氟西汀（５，２０ｍｇ·ｋｇ－１）慢性给药（ｉｐ每日１次，连续７ｄ）对大鼠游泳不动时间和下丘脑核团ｃ－Ｆｏｓ蛋白表达水平的影响．结果表明：强迫游泳可使大鼠下丘脑多个核团的ｃ－Ｆｏｓ蛋白表达水平明显升高，而地昔帕明，吗氯贝胺，氟西汀明显缩短强迫游泳大鼠的不动时间，并选择性地使强迫游泳诱导增加的下丘脑室旁核Ｆｏｓ样免疫阳性神经元数目明显减少．提示下丘脑室旁核可能是介导抗抑郁剂抑制大鼠绝望行为的中枢部位之一．

The effects of various antidepressants on the accumulated immobility time and the stressinduced cFos protein expression in forcedswimming rats were investigated by immunohistochemical method for localization of cFos protein. Rats were treated chronically ( ip daily for 7 days ) with desipramine ( 5, 20 mg·kg1 ), moclobemide ( 10, 40 mg·kg1) or fluoxetine ( 5, 20 mg·kg1), and exposed acutely to forcedswimming stress. The results indicated that forcedswimming stress increased significantly the number of Foslike immunoreactivity (irFos) neuron at hypothalamus. Both the suppression of the accumulated immobility time and the downregulation of cFos expression induced by forcedswimming stress selectively at hypothalamic paraventricular nucleus were observed with chronic administration of desipramine, moclobemide or fluoxetine. The results suggest that hypothalamic paraventricular nucleus may be one of the structural substrates in central nervous system mediating the antidepressive effects of different antidepressants on behavioral despair in forcedswimming rat, and that cFos protein may be a common substance of the signal transduction process for postreceptor action of antidepressant.