Bolaños Carlos A, Barrot Michel, Berton Olivier, Wallace-Black Deanna, Nestler Eric J
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Biol Psychiatry. 2003 Dec 15;54(12):1317-29. doi: 10.1016/s0006-3223(03)00570-5.
Methylphenidate (MPH) is a psychomotor stimulant medication widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Given the extent of prescribed use of MPH, and because MPH interacts with the same brain pathways activated by drugs of abuse, most research has focused on assessing MPH's potential to alter an individual's risk for adult drug addiction. Data examining other potential long-term behavioral consequences of early MPH administration are lacking, however.
We investigated the long-term behavioral consequences of chronic administration of MPH (2.0 mg/kg) during pre- and periadolescent development in adult rats by assessing their behavioral reactivity to a variety of emotional stimuli.
The MPH-treated animals were significantly less responsive to natural rewards such as sucrose, novelty-induced activity, and sex compared with vehicle-treated control animals. In contrast, MPH-treated animals were significantly more sensitive to stressful situations, showed increased anxiety-like behaviors, and had enhanced plasma levels of corticosterone.
Chronic exposure to MPH during development leads to decreased sensitivity to rewarding stimuli and results in enhanced responsivity to aversive situations. These results highlight the need for further research to improve understanding of the effects of stimulants on the developing nervous system and the potential enduring effects resulting from early-life drug exposure.
哌甲酯(MPH)是一种精神运动兴奋剂,广泛用于治疗注意力缺陷多动障碍(ADHD)。鉴于MPH的处方使用范围,并且由于MPH与滥用药物激活的相同脑通路相互作用,大多数研究都集中在评估MPH改变个体成年药物成瘾风险的潜力。然而,缺乏研究早期给予MPH的其他潜在长期行为后果的数据。
我们通过评估成年大鼠对各种情绪刺激的行为反应性,研究了在青春期前和青春期期间慢性给予MPH(2.0mg/kg)的长期行为后果。
与给予赋形剂的对照动物相比,接受MPH治疗的动物对蔗糖、新奇诱导的活动和性行为等自然奖励的反应明显降低。相比之下,接受MPH治疗的动物对压力情况明显更敏感,表现出增加的焦虑样行为,并且血浆皮质酮水平升高。
发育期间长期接触MPH会导致对奖励刺激的敏感性降低,并导致对厌恶情况的反应性增强。这些结果凸显了进一步研究的必要性,以增进对兴奋剂对发育中神经系统的影响以及早期药物暴露可能产生的持久影响的理解。