PDF(Pubmed)
Abstract：
P2X7 receptors are dysregulated during psychostimulant exposure. Furthermore, P2X7 receptors enhance endogenous systems (e.g., cytokines, dopamine, and glutamate) that facilitate psychostimulant addiction. Therefore, using mouse locomotor, conditioned place preference (CPP), and intracranial self-stimulation (ICSS) assays, we tested the hypothesis that methamphetamine (METH) reward and acute locomotor activation requires P2X7 receptor activity. We also investigated effects of P2X7 blockade on METH-induced changes in cytokine levels in brain reward regions. A438079 (5, 10, 50 mg/kg), a P2X7 antagonist, did not affect spontaneous locomotor activity but reduced hyperlocomotion caused by acute METH (1 mg/kg) exposure. A438079 (10 mg/kg) also prevented expression of METH CPP without causing aversive or rewarding effects. For ICSS experiments, METH (1 mg/kg) facilitated brain reward function as interpreted from reductions in baseline threshold. In the presence of A438079 (50 mg/kg), METH-induced facilitation of ICSS was reduced. Repeated METH exposure (1 mg/kg × 7 d) caused enhancement of IL-17A levels in the prefrontal cortex (PFC) that was normalized by A438070 (10 mg/kg × 7 d). The present data suggest that P2X7 receptor activity contributes to rewarding and locomotor-stimulant effects of METH through a potential mechanism involving IL-17A, which has recently been implicated in anxiety.
摘要：
P2X7受体在精神兴奋剂暴露期间失调。此外，P2X7受体增强内源性系统(例如，细胞因子,多巴胺,和谷氨酸）促进精神兴奋剂成瘾。因此,使用鼠标运动，条件位置偏好(CPP)，和颅内自我刺激（ICSS）测定，我们检验了以下假设:甲基苯丙胺(METH)奖励和急性运动激活需要P2X7受体活性.我们还研究了P2X7阻断对METH诱导的脑奖励区细胞因子水平变化的影响。A438079（5、10、50mg/kg），P2X7拮抗剂，不影响自发运动活动，但减少急性METH（1mg/kg）暴露引起的过度运动。A438079（10mg/kg）还可以防止METHCPP的表达，而不会引起厌恶或奖励作用。对于ICSS实验，METH（1mg/kg）促进了大脑奖励功能，从基线阈值的降低可以解释。在A438079（50mg/kg）的存在下，METH诱导的ICSS促进作用降低。重复的METH暴露（1mg/kg×7d）导致前额叶皮质（PFC）中IL-17A水平的升高，该水平已通过A438070（10mg/kg×7d）标准化。目前的数据表明，P2X7受体活性通过涉及IL-17A的潜在机制有助于METH的奖励和运动刺激作用，最近与焦虑有关。
