Enduring behavioral effects of early exposure to methylphenidate in rats
Enduring behavioral effects of early exposure to methylphenidate in rats
复制标题
DOI：
10.1016/j.biopsych.2003.08.020
复制
发表时间：
2003-12-15
影响因子：
10.6
通讯作者：
Andersen, SL
中科院分区：
文献类型：
--
作者：
Carlezon, WA;Mague, SD;Andersen, SL
背景：哌甲酯（MPH）是一种用于治疗注意力缺陷/多动障碍（ADHD）的兴奋剂。兴奋剂药物可以引起实验动物持久的行为适应，包括改变药物敏感性。我们研究了几种啮齿动物模型中早期发育接触兴奋剂如何影响行为。方法：大鼠在青春期前接受 MPH 或可卡因 (P20-35)。行为研究从成年时期开始（P60）。我们使用位置条件作用比较了早期接触 MPH 和可卡因如何影响对可卡因的奖励和厌恶特性的敏感性。我们还通过强迫游泳测试和活动室中自发运动的习惯化来检查早期接触 MPH 对抑郁样症状的影响。结果：在场所调节测试中，早期接触 MPH 或可卡因都会使中等剂量的可卡因产生厌恶感，而高剂量的可卡因则效果较差。早期接触 MPH 也会在强迫游泳测试中引起类似抑郁的效果，并减弱对活动室的习惯。结论：早期接触 MPH 会导致大鼠行为发生变化，这种变化会持续到成年期。一些变化（对可卡因奖励的敏感性降低）可能是有益的，而另一些变化（抑郁样症状的增加、习惯性的减少）可能是有害的。 MPH 对可卡因相关行为的影响可能是早期接触兴奋剂的普遍后果。
Background: Methylphenidate (MPH) is a stimulant prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulant drugs can cause enduring behavioral adaptations, including altered drug sensitivity, in laboratory animals. We examined how early developmental exposure to stimulants affects behavior in several rodent models.Methods: Rats received MPH or cocaine during preadolescence (P20-35). Behavioral studies began during adulthood (P60). We compared how early exposure to MPH and cocaine affects sensitivity to the rewarding and aversive properties of cocaine using place conditioning. We also examined the effects of early exposure to MPH on depressive-like signs using the forced swim test, and habituation of spontaneous locomotion, within activity chambers.Results: In place-conditioning tests, early exposure to MPH or cocaine each made moderate doses of cocaine aversive and high doses less rewarding. Early MPH exposure also caused depressive-like effects in the forced swim test, and it attenuated habituation to the activity chambers.Conclusions: Early exposure to MPH causes behavioral changes in rats that endure into adulthood. Some changes (reduced sensitivity to cocaine reward) may be beneficial, whereas others (increases in depressive-like signs, reduced habituation) may be detrimental. The effects of MPH on cocaine-related behaviors may be a general consequence of early stimulant exposure.