Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.
Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.
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DOI：
10.1016/j.brainresbull.2014.02.002
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Perrotti LI
中科院分区：
文献类型：
--
作者：
Bobzean SA;Dennis TS;Perrotti LI
与男性相比，女性和雌性啮齿动物对滥用精神兴奋剂药物的主观影响更敏感。越来越多的文献支持雌二醇作为这些性别差异的机制。然而，很少有人知道急性雌二醇水平升高对药物条件行为的影响。本研究的目的是评估急性增加全身雌二醇水平对可卡因条件性位置偏爱（CPP）表达的影响。使用6天的条件化程序，卵巢切除（OVX）雌性大鼠用四种剂量的可卡因（2.5、5、10或15 mg/kg）中的一种进行条件化，以使CPP装置的两个大室中的一个与可卡因或盐水相关联。在CPP偏好试验开始前30分钟，用5 μg苯甲酸雌二醇（EB）或花生油（PO）预处理大鼠。PO-处理的大鼠仅对中等调节剂量的可卡因（5和10 mg/kg）表现出显著偏好。然而，急性EB治疗导致可卡因剂量-反应曲线的显著偏移;大鼠仅在中等和高调节剂量的可卡因（10和15 mg/kg）下表现出显著偏好。这些研究结果表明，急性雌二醇升高可能会抑制条件反应的表达可卡因的二级奖励在较低的条件剂量的药物和促进CPP在较高的剂量，而雌二醇缺乏降低的阈值剂量的可卡因诱导CPP。
Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15 mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5 μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10 mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose-response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15 mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine’s secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.
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