Biopsychology and Behavioral Science Subprogram, Graduate Program in Psychology, Graduate Center of City University of New York, NY 10016, USA.
Neurobiol Learn Mem. 2010 Nov;94(4):488-98. doi: 10.1016/j.nlm.2010.08.016. Epub 2010 Sep 7.
Effects of estradiol benzoate (EB), ERα-selective agonist, propyl pyrazole triol (PPT) and ERβ-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2-4h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ERβ contribute to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60-130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40-80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ERβ mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus.
用物体识别（OR）和位置（OP）记忆任务，研究苯甲酸雌二醇（EB），雌激素受体α 选择性激动剂丙基吡唑三醇（PPT）和雌激素受体β 选择性激动剂二苯丙腈（DPN）和化合物 19（C-19）对去卵巢大鼠记忆的影响。处理是急性（行为后 4 小时）或亚慢性（每日注射 2 天，行为后 48 小时）。在样品试验（T1）中，物体被探索，在 2-4 小时的试验间隔后，在识别试验（T2）中，样品（旧）和新物体/位置之间的区分被检查。亚慢性处理 EB、DPN 和 C-19 的动物可以区分新旧物体和新旧位置，表明在这些剂量和治疗持续时间下，雌激素与 ERβ 的相互作用有助于增强识别记忆。在 T1 后立即给予急性注射 DPN，但不是 PPT，也增强了两个任务的辨别力（C19 未进行研究）。用高架十字迷宫和旷场测量的 EB、DPN 和 PPT 对焦虑和运动的影响，似乎没有解释记忆增强。在没有进行行为测试的动物中，测量了 DPN 处理后单胺和代谢物。DPN 与几种大脑区域的单胺改变有关：以代谢物 3-甲氧基-4-羟基苯乙二醇（MHPG）或 MHPG/去甲肾上腺素（NE）的比值为指标，前额叶皮层（PFC）和腹侧海马的 NE 活性增加 60-130%，而 v. 斜带和 CA1 的 NE 活性降低 40-80%。多巴胺（DA）代谢物高香草酸（HVA）的水平在 DPN 处理后增加 100%，在齿状回中降低 50%。5-羟色胺的代谢物 5-羟吲哚乙酸（5-HIAA）在 PFC 和 CA3 中增加约 20%。纹状体或中隔内未观察到单胺能变化。结果表明，ERβ 介导雌激素对识别记忆的亚慢性和急性作用，DPN 的记忆增强可能部分通过 PFC 和海马中主要的单胺能系统的改变发生。
