Walf Alicia A, Rhodes Madeline E, Frye Cheryl A
Department of Psychology, The University at Albany-SUNY, Albany, NY, USA.
Neurobiol Learn Mem. 2006 Jul;86(1):35-46. doi: 10.1016/j.nlm.2006.01.004. Epub 2006 Mar 10.
Learning and memory processes may be influenced by fluctuations in steroid hormones, such as estrogens and progestins. In this study, we have used an animal model to investigate the effects of endogenous fluctuations in ovarian steroids in intact female rats and effects of administration of ovarian steroids to ovariectomized rats for non-spatial, working memory using the object recognition task. Performance in this task relies on cortical and hippocampal function. As such, serum, cortical, and hippocampal concentrations of estradiol (E2), progesterone (P4), and P4's metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), were measured by radioimmunoassay. Experiment 1: Rats in behavioral estrus, compared to those in diestrus or estrus, spent a greater percentage of time exploring a novel object concomitant with increases in serum E2, P4, and 3alpha,5alpha-THP levels. Regression analyses revealed that there was a significant positive relationship between E2 levels in the hippocampus and 3alpha,5alpha-THP levels in the hippocampus and cortex and performance in this task. Experiment 2: Administration of E2 and/or P4 immediately post-training increased the percentage of time spent exploring the novel object and produced levels of E2, P4, and 3alpha,5alpha-THP akin to that of rats in behavioral estrus. Experiment 3: Post-training administration of selective estrogen receptor modulators, including 17beta-E2, propyl pyrazole triol, and diarylpropionitrile increased the percentage of time spent exploring the novel object compared to vehicle-administration. Experiment 4: Post-training P4 or 3alpha,5alpha-THP administration, compared to vehicle, increased the percentage of time spent exploring the novel object and produced P4 and/or 3alpha,5alpha-THP levels within the physiological range typically observed for rats in behavioral estrus. Experiment 5: If post-training administration of E2 and/or P4 was delayed one hour, no enhancement in object recognition was observed. Together, these results suggest that E2 and progestins can have mnemonic effects through actions in the cortex and/or hippocampus.
学习和记忆过程可能会受到类固醇激素波动的影响，比如雌激素和孕激素。在本研究中，我们使用动物模型来研究完整雌性大鼠体内卵巢类固醇的内源性波动的影响，以及对卵巢切除大鼠给予卵巢类固醇对非空间工作记忆的影响，采用物体识别任务进行研究。该任务的表现依赖于皮质和海马体功能。因此，通过放射免疫分析法测定了血清、皮质和海马体中雌二醇（E2）、孕酮（P4）以及P4的代谢产物5α-孕烷-3α-醇-20-酮（3α,5α-THP）的浓度。实验1：处于行为发情期的大鼠与处于动情间期或发情期的大鼠相比，探索新物体的时间占比更高，同时血清E2、P4和3α,5α-THP水平升高。回归分析显示，海马体中E2水平与海马体和皮质中3α,5α-THP水平以及该任务的表现之间存在显著正相关。实验2：训练后立即给予E2和/或P4增加了探索新物体的时间占比，并产生了与处于行为发情期的大鼠类似的E2、P4和3α,5α-THP水平。实验3：训练后给予选择性雌激素受体调节剂，包括17β-E2、丙基吡唑三醇和二芳基丙腈，与给予赋形剂相比，增加了探索新物体的时间占比。实验4：训练后给予P4或3α,5α-THP，与给予赋形剂相比；增加了探索新物体的时间占比，并产生了行为发情期大鼠通常观察到的生理范围内的P4和/或3α,5α-THP水平。实验5：如果训练后给予E2和/或P4延迟一小时，则未观察到物体识别能力增强。总之，这些结果表明E2和孕激素可通过在皮质和/或海马体中的作用产生记忆效应。
