Bowles Center for Alcohol Studies, University of North Carolina Chapel Hill, NC, USA.
Front Integr Neurosci. 2011 Oct 14;5:63. doi: 10.3389/fnint.2011.00063. eCollection 2011.
Sex differences in the rapid and acute effects of estradiol on time perception were investigated in adult male and female Sprague-Dawley rats. Because estradiol has been shown to increase striatal dopamine release, it may be able to modify time perception and timed performance by increasing the speed of an internal clock in a manner similar to indirect dopamine agonists such as amphetamine and cocaine. Two groups of females (neonatally estradiol-treated/adult ovariectomized and neonatally oil-treated/adult ovariectomized) and two groups of males (neonatally castrated and adult castrated) were trained in a 2 vs. 8-s duration bisection procedure and tested using intermediate signal durations. After obtaining oil-injected baseline psychometric functions over several days, rats were administered 5 μg of estradiol for 4 days and behaviorally evaluated 30 min following each injection. This oil-estradiol administration cycle was subsequently repeated three times following the re-establishment of baseline training. Results revealed significant sex differences in the initial baseline functions that were not modifiable by organizational hormones, with males' duration bisection functions shifted horizontally to the left of females'. Upon the first administration of estradiol, females, but not males, showed a significant, transient leftward shift in their bisection functions, indicative of an increase in clock speed. After extensive retraining in the duration bisection procedure, rats that were exposed to gonadal hormones during the first week of life showed a significant rightward shift in their bisection functions on the fourth day of estradiol administration during each cycle, suggesting a decrease in clock speed. Taken together, our results support the view that there are multiple mechanisms of estrogens' action in the striatum that modulate dopaminergic activity and are differentially organized by gonadal steroids during early brain development.
本研究旨在探究雌二醇对成年雄性和雌性斯普拉格-道莱（Sprague-Dawley）大鼠时间知觉的快速、急性影响是否存在性别差异。由于雌二醇已被证实可增加纹状体多巴胺的释放，因此它可能通过以类似于安非他命和可卡因等间接多巴胺激动剂的方式来增加内部时钟的速度，从而改变时间知觉和定时表现。我们训练了两组雌性大鼠（出生时接受雌二醇处理/成年时卵巢切除术和出生时接受油处理/成年时卵巢切除术）和两组雄性大鼠（出生时去势/成年时去势），并在 2 对 8 秒持续时间二分法程序中进行训练，并使用中间信号持续时间进行测试。在获得数天的油注射基准心理物理函数后，大鼠接受 5μg 雌二醇连续 4 天注射，并在每次注射后 30 分钟进行行为评估。在重新建立基准训练后，重复该油-雌二醇给药周期三次。结果显示，在初始基准函数中存在显著的性别差异，这些差异不受组织激素的影响，雄性的持续时间二分法函数向左移，位于雌性函数的左侧。第一次给予雌二醇时，只有雌性大鼠而非雄性大鼠的二分法函数出现显著、短暂的向左移动，表明时钟速度增加。在持续时间二分法程序的广泛重新训练后，在生命的第一周接触性腺激素的大鼠在每个周期的第四天雌二醇给药时其二分法函数出现显著的右移，表明时钟速度降低。总的来说，我们的结果支持这样一种观点，即雌二醇在纹状体中的作用机制有多种，可调节多巴胺活性，并在大脑早期发育过程中被性腺类固醇以不同的方式组织。
