Mnemonic effects of testosterone and its 5α-reduced metabolites in the conditioned fear and inhibitory avoidance tasks
Mnemonic effects of testosterone and its 5α-reduced metabolites in the conditioned fear and inhibitory avoidance tasks
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DOI：
10.1016/j.pbb.2004.04.024
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Frye, CA
中科院分区：
文献类型：
--
作者：
Edinger, KL;Lee, B;Frye, CA
本实验旨在研究睾酮（T）和/或其5 α还原代谢产物双氢睾酮（DHT）和3 α-雄甾烷酮（3 α-diol）是否影响大鼠在脑内介导的学习任务中的表现。在条件性恐惧和抑制性回避任务的性能进行了检查，在完整的和性腺切除（GDX），雄激素替代大鼠。实验一比较了正常大鼠和GDX大鼠在条件性恐惧范式中的行为。GDX大鼠花更多的时间冻结，增加学习的指标，在上下文中，杏仁核介导的任务，但不是在线索，杏仁核介导的任务。在实验2中，GDX大鼠在条件性恐惧范例中训练后皮下给予T、DHT、3 α-二醇、雌激素（E-2）或载体1 mg/kg。T-，3 α-二醇，或E-2-，与车辆管理的大鼠相比，花了更多的时间冻结在上下文，但不是线索，条件。在实验3中，与GDX大鼠相比，完整的有显着更长的交叉潜伏期，表明更好的性能，在抑制性回避任务。在实验4中，T，DHT，3 α-二醇，或车辆1毫克/公斤sc GDX大鼠训练后立即在抑制性回避任务。与溶剂对照组相比，给予T、DHT或3 α-二醇的大鼠交叉潜伏期显著延长。在实验5中，雄激素水平在海马升高1小时后给药，雄激素暴露是必不可少的巩固。这些数据表明，雄激素增强学习的作用可能部分是通过海马体中5 α还原代谢物的作用介导的。(C)2004年爱思唯尔公司All rights reserved.
Experiments were conducted to examine whether performance in hippocampally mediated learning tasks is influenced by testosterone (T) and/or its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and 3alpha-androstanediol (3alpha-diol). Performance in the conditioned fear and inhibitory avoidance tasks were examined in intact and gonadectomized (GDX), androgen-replaced rats. In Experiment 1, the behavior of intact and GDX rats in the conditioned fear paradigm were compared. GDX rats spent more time freezing, an index of increased learning, in the context, hippocampally-mediated task, but not in the cued, amygdala-mediated task. In Experiment 2, GDX rats were administered T, DHT, 3alpha-diol, estrogen (E-2), or vehicle 1 mg/kg sc after training in the conditioned fear paradigm. T-, 3aalpha-diol-, or E-2-, compared with vehicle-administered rats, spent significantly more time freezing in the contextual, but not the cued, condition. In Experiment 3, intact compared with GDX rats had significantly longer crossover latencies, indicating better performance, in the inhibitory avoidance task. In Experiment 4, T, DHT, 3alpha-diol, or vehicle 1 mg/kg sc was administered to GDX rats immediately following training in the inhibitory avoidance task. Rats administered T, DHT, or 3alpha-diol had significantly longer crossover latencies compared with vehicle controls. In Experiment 5, androgen levels in the hippocampus were elevated 1 h following administration, when androgen exposure is essential for consolidation. These data indicate that androgens effects to enhance learning may be mediated in part by actions of 5alpha-reduced metabolites in the hippocampus. (C) 2004 Elsevier Inc. All rights reserved.