Tajik Azam, Rezayof Ameneh, Ghasemzadeh Zahra, Sardari Maryam
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
Neuroscience. 2016 Jul 7;327:1-9. doi: 10.1016/j.neuroscience.2016.04.008. Epub 2016 Apr 9.
Tamoxifen (TAM), a selective estrogen receptor modulator, has frequently been used in the treatment of breast cancer. In view of the fact that cognitive deficits in women who receive adjuvant chemotherapy for breast cancer is a common health problem, using female animal models for investigating the cognitive effects of TAM administration may improve our knowledge of TAM therapy. Therefore, the present study assessed the role of dorsal hippocampal cholinergic nicotinic receptors (nAChRs) in the effect of TAM administration on memory retrieval in ovariectomized (OVX) and non-OVX female rats using a passive avoidance learning task. Our results showed that pre-test administration of TAM (2-6mg/kg) impaired memory retrieval. Pre-test intra-CA1 microinjection of nicotine (0.3-0.5μg/rat) reversed TAM-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (0.1-0.3μg/rat) plus 2mg/kg (an ineffective dose) of TAM impaired memory retrieval. Pre-test intra-CA1 microinjection of the same doses of nicotine and mecamylamine by themselves had no effect on memory retrieval. In OVX rats, the administration of TAM (6mg/kg) produced memory impairment but pre-test intra-CA1 microinjection of nicotine (0.5μg/rat) had no effect on TAM response. Moreover, the administration of an ineffective dose of TAM (2mg/kg) had no effect on memory retrieval in OVX rats, while pre-test intra-CA1 microinjection of mecamylamine (0.3μg/rat) impaired memory retrieval. Taken together, it can be concluded that the impairing effect of TAM on memory formation may be modulated by nAChRs of the CA1 regions. It seems that memory impairment may be considered as an important side effect of TAM.
他莫昔芬（TAM）是一种选择性雌激素受体调节剂，常用于治疗乳腺癌。鉴于接受乳腺癌辅助化疗的女性存在认知缺陷这一常见健康问题，利用雌性动物模型研究TAM给药的认知效应可能会增进我们对TAM治疗的了解。因此，本研究使用被动回避学习任务，评估了背侧海马胆碱能烟碱受体（nAChRs）在TAM给药对去卵巢（OVX）和未去卵巢雌性大鼠记忆提取影响中的作用。我们的结果表明，预测试给予TAM（2 - 6mg/kg）会损害记忆提取。预测试在CA1区域内微量注射尼古丁（0.3 - 0.5μg/只大鼠）可逆转TAM诱导的记忆损伤。预测试在CA1区域内微量注射美加明（0.1 - 0.3μg/只大鼠）加2mg/kg（无效剂量）的TAM会损害记忆提取。预测试在CA1区域内微量注射相同剂量的尼古丁和美加明本身对记忆提取没有影响。在OVX大鼠中，给予TAM（6mg/kg）会产生记忆损伤，但预测试在CA1区域内微量注射尼古丁（0.5μg/只大鼠）对TAM的反应没有影响。此外，给予无效剂量的TAM（2mg/kg）对OVX大鼠的记忆提取没有影响，而预测试在CA1区域内微量注射美加明（0.3μg/只大鼠）会损害记忆提取。综上所述，可以得出结论，TAM对记忆形成的损害作用可能受CA1区域的nAChRs调节。似乎记忆损伤可能被视为TAM的一种重要副作用。
