Carlezon William A, Mague Stephen D, Andersen Susan L
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.
Biol Psychiatry. 2003 Dec 15;54(12):1330-7. doi: 10.1016/j.biopsych.2003.08.020.
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.
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.
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.
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.
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。在实验动物中,兴奋剂药物可导致持久的行为适应性改变,包括药物敏感性改变。我们研究了早期发育阶段接触兴奋剂如何影响几种啮齿动物模型的行为。
大鼠在青春期前(P20 - 35)接受MPH或可卡因。行为研究在成年期(P60)开始。我们使用位置条件反射比较早期接触MPH和可卡因如何影响对可卡因奖赏性和厌恶性特性的敏感性。我们还使用强迫游泳试验以及在活动箱内对自发运动的习惯化来研究早期接触MPH对抑郁样症状的影响。
在位置条件反射试验中,早期接触MPH或可卡因均使中等剂量的可卡因具有厌恶性,高剂量的可卡因奖赏性降低。早期接触MPH在强迫游泳试验中也导致了抑郁样效应,并且减弱了对活动箱的习惯化。
早期接触MPH会导致大鼠的行为变化持续到成年期。一些变化(对可卡因奖赏的敏感性降低)可能是有益的,而其他变化(抑郁样症状增加、习惯化减弱)可能是有害的。MPH对与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。