Pre-administration of low-dose methamphetamine enhances movement and neural activity after high-dose methamphetamine administration in the striatum
Pre-administration of low-dose methamphetamine enhances movement and neural activity after high-dose methamphetamine administration in the striatum
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DOI：
10.1016/j.neulet.2019.03.023
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发表时间：
2019-06
影响因子：
2.5
通讯作者：
T. Takeichi;O. Hori;T. Hattori;Kyoka Kiryu;Masahiko Zuka;O. Kitamura
中科院分区：
文献类型：
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作者：
T. Takeichi;O. Hori;T. Hattori;Kyoka Kiryu;Masahiko Zuka;O. Kitamura
甲基苯丙胺（METH）是一种强有力的兴奋剂滥用药物，具有强烈的成瘾性和神经毒性。在这项研究中，在高剂量METH给药之前给药低剂量METH对大鼠运动和神经活动的影响进行了检查。大鼠连续5天（分别为m5和s5）给予低剂量（1 mg/kg/天）METH或盐水，然后在第6天（分别为m5 M和s5 M）给予高剂量（10 mg/kg）METH。使用加速度计评估大鼠在笼中放置30 min时的运动频率。采用免疫组织化学方法分析纹状体中神经元活性标记物c-fos的表达。通过蛋白质印迹分析神经元标记物的纹状体蛋白表达，包括囊泡谷氨酸转运体2（VGLUT 2）、谷氨酸脱羧酶67（GAD 67）、酪氨酸羟化酶（TH）、色氨酸羟化酶2（TPH 2）和胶质细胞标记物胶质细胞酸性蛋白（GFAP）。加速度计计数和c-fos阳性细胞在纹状体的数量显着高于在s5，m5，和s5 M组的m5 M。VGLUT 2和GAD 67的表达水平在m5 M组中显著高于s5 M组，而TH、TPH 2或GFAP的表达水平则无显著差异。这些结果表明，在大鼠中高剂量METH给药之前预给药低剂量METH可能会改变纹状体中的兴奋性和抑制性神经元，从而影响大鼠的运动和神经活动。
Methamphetamine (METH) is a powerful stimulant drug of abuse, with potent addictive and neurotoxic properties. In this study, the effects of low-dose METH administration prior to high-dose METH administration on movement and neural activity in rats were examined. Rats were administered low-dose (1 mg/kg/day) METH or saline for 5 consecutive days (m5 and s5, respectively), followed by high-dose (10 mg/kg) METH on day 6 (m5M and s5M, respectively). An accelerometer was used to evaluate the frequency of movement when rats were placed in a cage for 30 min. The expression of c-fos, a neuronal activity marker, in the striatum was analyzed using immunohistochemistry. Striatal protein expression of neuronal markers, including vesicular glutamate transporter 2 (VGLUT2), glutamate decarboxylase 67 (GAD67), tyrosine hydroxylase (TH), tryptophan hydroxylase 2 (TPH2), and the glial marker, glial fibrillary acidic protein (GFAP), was analyzed by western blot. Accelerometer counts and the numbers of c-fos-positive cells in the striatum were significantly higher in the m5M than in the s5, m5, and s5M groups. The expression levels of VGLUT2 and GAD67, but not those of TH, TPH2, or GFAP, were significantly higher in the m5M than in the s5M group. These results suggest that pre-administration of low-dose METH prior to high-dose METH administration in rats may alter excitatory and inhibitory neurons in the striatum, thereby affecting movement and neural activity in rats.