Almeida Rúbia C, Souza Daniela G, Soletti Rossana C, López Manuela G, Rodrigues Ana Lúcia S, Gabilan Nelson H
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
Neurosci Lett. 2006 Mar 6;395(2):93-7. doi: 10.1016/j.neulet.2005.10.057. Epub 2005 Nov 14.
This study investigated the cellular signaling pathways involved in the acute antidepressant-like action of memantine in the forced swimming test (FST) in mice. The immobility time in the FST was reduced by memantine (3-10 mg/kg, i.p.). The anti-immobility effect of memantine (3 mg/kg, i.p.) was prevented by pretreatment with H-89 (1 microg/site, i.c.v., an inhibitor of PKA), PD098059 (5 microg/site, i.c.v., an inhibitor of MAPK/ERK), KN-62 (1 microg/site, i.c.v., an inhibitor of CaMKII), but not with chelerythrine (1 microg/site, i.c.v., an inhibitor of PKC). Taken together, these results firstly demonstrate that the acute antidepressant-like effect of memantine seems to be dependent on the cellular signaling modulated by PKA, CaMKII and MAPK/ERK, but not by PKC.
本研究调查了美金刚在小鼠强迫游泳试验（FST）中急性抗抑郁样作用所涉及的细胞信号通路。美金刚（3 - 10毫克/千克，腹腔注射）可减少FST中的不动时间。H - 89（1微克/部位，脑室内注射，蛋白激酶A抑制剂）、PD098059（5微克/部位，脑室内注射，丝裂原活化蛋白激酶/细胞外信号调节激酶抑制剂）、KN - 62（1微克/部位，脑室内注射，钙/钙调蛋白依赖性蛋白激酶II抑制剂）预处理可阻断美金刚（3毫克/千克，腹腔注射）的抗不动作用，但白屈菜红碱（1微克/部位，脑室内注射，蛋白激酶C抑制剂）预处理则不能。综上所述，这些结果首次表明，美金刚的急性抗抑郁样作用似乎依赖于由蛋白激酶A、钙/钙调蛋白依赖性蛋白激酶II和丝裂原活化蛋白激酶/细胞外信号调节激酶介导的细胞信号传导，而非蛋白激酶C。
