Methylphenidate (MPD) is commonly used to treat attention-deficit hyperactivity disorder (ADHD). Recently, it is being abused for cognitive enhancement and recreation leading to concerns regarding its addictive potential. The prefrontal cortex (PFC) and caudate nucleus (CN) are two of the brain structures involved in the motive/reward circuit most affected by MPD and are also thought to be responsible for ADHD phenomena. This study is unique in that it investigated acute and chronic, dose-response MPD exposure on animals' behavior activity concomitantly with PFC and CN neuronal circuitry in freely behaving adult animals without the interference of anesthesia. Further, it compared acute and chronic MPD action on over 1,000 subcortical and cortical neurons simultaneously, allowing for a more accurate interpretation of drug action on corticostriatal neuronal circuitry. For this experiment, four groups of animals were used: saline (control), 0.6, 2.5, and 10.0 mg/kg MPD following acute and repetitive exposure. The data shows that the same MPD dose elicits behavioral sensitization in some animals and tolerance in others and that the PFC and CN neuronal activity correlates with the animals' behavioral responses to MPD. The expression of sensitization and tolerance are experimental biomarkers indicating that a drug has addictive potential. In general, a greater percentage of CN units responded to both acute and chronic MPD exposure as compared to PFC units. Dose response differences between the PFC and the CN units were observed. The dichotomy that some PFC and CN units responded to the same MPD dose by excitation and other units by attenuation in neuronal firing rate is discussed. In conclusion, to understand the mechanism of action of the drug, it is essential to study, simultaneously, on more than one brain site, the electrophysiological and behavioral effects of acute and chronic drug exposure, as sensitization and tolerance are experimental biomarkers indicating that a drug has addictive potential. The behavioral and neuronal data obtained from this study indicates that chronic MPD exposure results in behavioral and biochemical changes consistent with a substance abuse disorder.

中文翻译：

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前额叶皮层和尾状核对哌甲酯（利他林）有共同反应。伴随的行为和神经元记录研究。

哌甲酯 (MPD) 通常用于治疗注意力缺陷多动障碍 (ADHD)。最近，它被滥用于认知增强和娱乐，导致对其成瘾潜力的担忧。前额叶皮层 (PFC) 和尾状核 (CN) 是参与受 MPD 影响最大的动机/奖励回路的两个大脑结构，也被认为是导致 ADHD 现象的原因。这项研究的独特之处在于它调查了急性和慢性、剂量反应 MPD 暴露对动物行为活动的影响，同时 PFC 和 CN 神经元回路在不受麻醉干扰的情况下自由行为的成年动物中。此外，它同时比较了 1,000 多个皮层下和皮层神经元的急性和慢性 MPD 作用，允许更准确地解释药物对皮质纹状体神经元回路的作用。对于该实验，使用了四组动物：盐水（对照），急性和重复暴露后的 0.6、2.5 和 10.0 mg/kg MPD。数据显示，相同的 MPD 剂量在某些动物中引起行为敏感，而在其他动物中引起耐受，并且 PFC 和 CN 神经元活动与动物对 MPD 的行为反应相关。致敏和耐受的表达是表明药物具有成瘾潜力的实验性生物标志物。一般而言，与 PFC 单位相比，更大百分比的 CN 单位对急性和慢性 MPD 暴露有反应。观察到 PFC 和 CN 单位之间的剂量响应差异。讨论了一些 PFC 和 CN 单位通过激发对相同 MPD 剂量作出反应，而其他单位通过神经元放电率衰减对相同的 MPD 剂量作出反应的二分法。总之，要了解药物的作用机制，必须同时在多个大脑部位研究急性和慢性药物暴露的电生理和行为影响，因为敏化和耐受性是实验性生物标志物，表明药物具有成瘾的潜力。从这项研究中获得的行为和神经元数据表明，长期暴露于 MPD 会导致行为和生化变化，这与药物滥用障碍一致。在多个大脑部位，急性和慢性药物暴露的电生理和行为影响，如敏化和耐受性是表明药物具有成瘾潜力的实验性生物标志物。从这项研究中获得的行为和神经元数据表明，长期暴露于 MPD 会导致行为和生化变化，这与药物滥用障碍一致。在多个大脑部位，急性和慢性药物暴露的电生理和行为影响，如敏化和耐受性是表明药物具有成瘾潜力的实验性生物标志物。从这项研究中获得的行为和神经元数据表明，长期暴露于 MPD 会导致行为和生化变化，这与药物滥用障碍一致。