Brain processes in discounting: consequences of adolescent methylphenidate exposure.
Brain processes in discounting: consequences of adolescent methylphenidate exposure.
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DOI：
10.1007/7854_2011_156
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Laviola, Giovanni
中科院分区：
文献类型：
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作者：
Adriani, Walter;Zoratto, Francesca;Laviola, Giovanni
注意力不集中、冲动和运动多动的特征是被诊断为注意力缺陷/多动障碍(ADHD)的儿童的特征，他们的抑制控制能力降低。在动物模型中，关键的发育阶段或实验转基因条件解释了感觉寻求和冒险行为等特性，并复制了精神刺激剂的有益效果。当大鼠的前脑多巴胺(DA)系统发生重塑时，如青春期，或通过实验操作敲击多巴胺转运体(DAT)，大鼠的行为特征似乎更加冲动。利他林()(哌醋甲酯，MPH)是一种DAT阻断药物，用于ADHD治疗，但也被人类青少年广泛滥用。在大鼠青春期服用MPH会导致其自控力的长期调整，表现在减少了对拖延的不耐性，并减少了在回报不确定时对风险的倾向。当外源性DAT水平的改变是通过慢病毒转染法实现时，则会出现完全相反的情况。青春期MPH暴露和DAT靶向转基因均可导致纹状体背侧功能亢进和腹侧纹状体功能减退。加上前额叶皮质磷酸肌酸的上调，纹状体中选定的基因(如5-羟色胺7受体基因)的上调表明，青少年接触MPH会产生更强的抑制控制。操作任务评估动机驱动和抑制性自我控制之间的平衡，因此对于研究奖励折扣过程及其通过DAT目标工具的调节是有用的。综上所述，由于人类研究的复杂性，有必要对啮齿动物模型进行临床前研究，以更好地了解ADHD样症状的病因的神经生物学和青少年接触PMH的长期治疗安全性。
Traits of inattention, impulsivity, and motor hyperactivity characterize children diagnosed with attention-deficit/hyperactivity disorder (ADHD), whose inhibitory control is reduced. In animal models, crucial developmental phases or experimental transgenic conditions account for peculiarities, such as sensation-seeking and risk-taking behaviors, and reproduce the beneficial effects of psychostimulants. An "impulsive" behavioral profile appears to emerge more extremely in rats when forebrain dopamine (DA) systems undergo remodeling, as in adolescence, or with experimental manipulation tapping onto the dopamine transporter (DAT). Ritalin() (methylphenidate, MPH), a DAT-blocking drug, is prescribed for ADHD therapy but is also widely abused by human adolescents. Administration of MPH during rats' adolescence causes a long-term modulation of their self-control, in terms of reduced intolerance to delay and diminished proneness for risk when reward is uncertain. Exactly the opposite profile emerges when exogenous alteration of DAT levels is achieved via lentiviral transfection. Both adolescent MPH exposure and DAT-targeting transfection lead to enduring hyperfunction of dorsal striatum and hypofunction of ventral striatum. Together with upregulation of prefronto-cortical phospho-creatine, striatal upregulation of selected genes (like serotonin 7 receptor gene) suggests that enhanced inhibitory control is generated by adolescent MPH exposure. Operant tasks, which assess the balance between motivational drives and inhibitory self-control, are thus useful for investigating reward-discounting processes and their modulation by DAT-targeting tools. In summary, due to the complexity of human studies, preclinical investigations of rodent models are necessary to understand better both the neurobiology of ADHD-like symptoms' etiology and the long-term therapeutic safety of adolescent MPH exposure.