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Caudate neuronal recording in freely behaving animals following acute and chronic dose response methylphenidate exposure

机译：急性和慢性剂量反应哌醋甲酯暴露后自由行为动物的尾状神经元记录

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The misuse and abuse of the psychostimulant, methylphenidate (MPD) the drug of choice in the treatment of attention deficit hyperactivity disorder (ADHD) has seen a sharp uprising in recent years among both youth and adults for its cognitive enhancing effects and for recreational purposes. This uprise in illicit use has lead to many questions concerning the long term consequences of MPD exposure. The objective of this study was to record animal behavior concomitantly with the caudate nucleus (CN) neuronal activity following acute and repetitive (chronic) dose response exposure to methylphenidate (MPD). A saline control and three MPD dose (0.6, 2.5, and 10.0 mg/kg) groups were used.Behaviorally, the same MPD dose in some animals following chronic MPD exposure elicited behavioral sensitization and other animals elicited behavioral tolerance. Based on this finding, the CN neuronal population recorded from animals expressing behavioral sensitization were also evaluated separately from CN neurons recorded from animals expressing behavioral tolerance to chronic MPD exposure, respectively.Significant differences in CN neuronal population responses between the behaviorally sensitized and the behaviorally tolerant animals was observed for the 2.5 and 10.0 mg/kg MPD exposed groups. For 2.5 mg/kg MPD, behaviorally sensitized animals responded by decreasing their firing rates while behaviorally tolerant animals showed mainly an increase in their firing rates. The CN neuronal responses recorded from the behaviorally sensitized animals following 10.0 mg/kg MPD responded by increasing their firing rates whereas the CN neuronal recordings from the behaviorally tolerant animals showed that approximately half decreased their firing rates in response to 10.0 mg/kg MPD exposure. The comparison of percentage change in neuronal firing rates showed that the behaviorally tolerant animals trended to exhibit increases in their neuronal firing rates at ED1 following initial MPD exposure and oppositely at ED10 MPD rechallenge. While the behaviorally sensitized animals in general increased in their percentage change of firing rats were observed following acute 10.0 mg/kg MPD and the behaviorally sensitized 10.0 mg/kg MPD animals and a robust increase in neuronal firing rates at ED1 and ED10 rechallenge.These results suggest the need to first individually analyze animal behavioral activity, and than to evaluate the neuronal responses to the drug based on the animals behavioral response to chronic MPD exposure.
机译：精神兴奋剂哌醋甲酯（MPD）的滥用和滥用是治疗注意力缺陷多动障碍（ADHD）的首选药物，近年来，由于其认知增强作用和娱乐目的，青年和成年人均发生了急剧上升。非法使用的上升导致了许多有关MPD暴露的长期后果的问题。这项研究的目的是记录暴露于哌醋甲酯（MPD）的急性和重复（慢性）剂量反应后动物的行为以及尾状核（CN）的神经元活动。使用生理盐水对照组和三个MPD剂量组（0.6、2.5和10.0 mg / kg）。在行为上，某些MPD在长期暴露于MPD后引起行为敏化，而其他动物则引起行为耐受。基于这一发现，还分别评估了从表现出行为敏化的动物中记录的CN神经元种群与从表现出对慢性MPD暴露的行为耐受性的动物所记录的CN神经元的差异。观察2.5和10.0 mg / kg MPD暴露组的动物。对于2.5 mg / kg的MPD，行为敏化的动物会通过降低其放电率来做出反应，而行为宽容的动物则主要表现为其放电率增加。行为敏化动物在10.0 mg / kg MPD之后记录的CN神经元反应通过提高其放电率来响应，而行为耐受动物的CN神经元记录显示，响应于10.0 mg / kg MPD暴露，大约有一半的动物降低了放电率。对神经元放电率的百分比变化的比较表明，行为耐受性动物倾向于在初始MPD暴露后在ED1处表现出神经元放电率增加，而在ED10 MPD再挑战时表现出相反的变化。行为敏化动物通常在急性10.0 mg / kg MPD和行为敏化10.0 mg / kg MPD动物后观察到其放电大鼠的百分比变化增加，并且在ED1和ED10再攻击时神经元放电率显着增加。提示需要首先单独分析动物的行为活动，然后根据动物对慢性MPD暴露的行为反应评估对药物的神经元反应。

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