Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness
Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness
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DOI：
10.1016/j.biopsych.2008.04.037
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发表时间：
2008-10-01
影响因子：
10.6
通讯作者：
Berridge, Craig W.
中科院分区：
文献类型：
--
作者：
Devilbiss, David M.;Berridge, Craig W.
背景资料：尽管低剂量精神兴奋剂被广泛用于治疗注意力缺陷多动障碍（ADHD），但这些药物治疗作用的神经基础尚不清楚。我们最近证明，低剂量哌醋甲酯（MPH）增加儿茶酚胺流出优先在前额叶皮层（PFC），这表明PFC是一个主要的网站的行为镇静和认知增强作用的低剂量精神兴奋剂。为了更好地了解参与低剂量兴奋剂的行为动作的神经机制，本研究探讨了低剂量MPH对PFC神经元的个体和集合的放电特性的影响。方法：多个单独的PFC神经元的细胞外活动记录在自由移动的大鼠使用多通道记录技术。行为研究确定了最佳的，增强工作记忆的腹腔MPH剂量。将这些低剂量MPH对PFC神经元放电特性的影响与1）高剂量MPH对PFC神经元放电的影响和2）低剂量MPH对体感皮层内神经元放电的影响进行比较。只有工作记忆-增强MPH的剂量增加了单个PFC神经元的反应性，并改变了PFC内神经元的整体反应。PFC（即，在躯体感觉皮层内）。相比之下，高剂量MPH深刻抑制诱发放电的PFC neurons.Conclusions：这些观察表明，优先增强PFC内的信号处理，包括个别PFC神经元和PFC神经元合奏的放电特性的改变，是低剂量精神兴奋剂的行为/认知行动的基础。
Background: Despite widesread use of low-dose psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD), the neural basis for the therapeutic actions of these drugs are not well understood. We recently demonstrated that low-dose methylphenidate (MPH) increases catecholamine efflux preferentially within the prefrontal cortex (PFC), suggesting that the PFC is a principal site of action in the behavioral-calming and cognition-enhancing effects of low-dose psychostimulants. To understand better the neural mechanisms involved in the behavioral actions of low-dose stimulants, this study examined the effects of low-dose MPH on the discharge properties of individual and ensembles of PFC neurons.Methods: Extracellular activity of multiple individual PFC neurons was recorded in freely moving rats using multichannel recording techniques. Behavioral studies identified optimal, working memory-enhancing doses of intraperitoneal MPH. The effects of these low-doses of MPH on PFC neuronal discharge properties were compared with 1) the effects of high-dose MPH on PFC neuronal discharge and 2) the effects of low-dose MPH on neuronal discharge within the somatosensory cortex.Results: Only working memory-enhancing doses of MPH increased the responsivity of individual PFC neurons and altered neuronal ensemble responses within the PFC. These effects were not observed outside the PFC (i.e., within somatosensory cortex). In contrast, high-dose MPH profoundly suppressed evoked discharge of PFC neurons.Conclusions: These observations suggest that preferential enhancement of signal processing within the PFC, including alterations in the discharge properties of individual PFC neurons and PFC neuronal ensembles, underlie the behavioral/cognitive actions of low-dose psychostimulants.