Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats

摘要

In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective alpha 7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-beta-erythroidine, a selective alpha 4 beta 2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-beta-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal alpha 7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via alpha 7 nAChR and alpha 4 beta 2 nAChR, and also enhances hippocampal neurogenesis.