Nicotine alters striatal glutamate function and decreases the apomorphine-induced contralateral rotations in 6-OHDA-lesioned rats
Nicotine alters striatal glutamate function and decreases the apomorphine-induced contralateral rotations in 6-OHDA-lesioned rats
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DOI：
10.1006/exnr.2002.7900
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发表时间：
2002-05-01
影响因子：
5.3
通讯作者：
Krentz, L
中科院分区：
文献类型：
--
作者：
Meshul, CK;Kamel, D;Krentz, L
本研究的总体目标是确定亚慢性尼古丁(0.4 mg/kg)处理7天或14天对黑质纹状体多巴胺通路受损的幼鼠和6-羟基多巴胺(6-OHDA)处理的大鼠纹状体谷氨酸功能的影响。在受损动物中，还评估了尼古丁对阿朴吗啡诱导的对侧旋转的影响。在幼鼠中，与生理盐水组相比，每日一次尼古丁连续给药7天或14天，纹状体细胞外谷氨酸的基础水平分别降低和升高。在超微结构上，尼古丁处理14天后，与生理盐水处理组相比，纹状体谷氨酸免疫标记神经末梢的密度增加，形成不对称的突触接触。在6-OHDA损毁动物中，尼古丁与阿朴吗啡或尼古丁单独联合给药7天，与阿朴吗啡或生理盐水组相比，神经末梢谷氨酸免疫标记密度增加。然而，与尼古丁治疗组相比，尼古丁和阿朴吗啡联合给药14天后，神经末梢谷氨酸免疫标记密度降低。亚慢性阿朴吗啡治疗6-羟色胺损伤大鼠7天或14天后，与生理盐水组相比，阿朴吗啡诱导的对侧旋转次数增加。与阿朴吗啡治疗组相比，尼古丁和阿朴吗啡联合用药7天或14天组阿朴吗啡诱导的对侧旋转次数减少。数据表明，在帕金森病的6-OHDA损伤模型中，尼古丁治疗可能有助于抵消用阿朴吗啡等多巴胺激动剂治疗后观察到的增加的行为效应(即对侧旋转)。(C)2002年埃尔塞维尔科学公司(美国)。
The overall goal of this study was to determine the effects of subchronic nicotine (0.4 mg/kg) treatment for 7 or 14 days on striatal glutamate function in both naive and in 6-hydroxydopamine (6-OHDA)-treated rats in which the nigrostriatal dopamine pathway was lesioned. In lesioned animals, the effect of nicotine on apomorphine-induced contralateral rotations was also assessed. In naive rats, once daily nicotine administration for 7 or 14 days resulted in a decrease and then an increase, respectively, in the basal extracellular level of striatal glutamate compared to the saline-treated group. Ultrastructurally, 14-day treatment with nicotine resulted in an increase in the density of striatal glutamate immunolabeling within nerve terminals making an asymmetrical synaptic contact compared to the saline-treated group. In 6-OHDA-lesioned animals, coadministration of nicotine with apomorphine or nicotine alone for 7 days resulted in an increase in the density of nerve terminal glutamate immunolabeling, compared to the apomorphine- or saline-treated groups. However, coadministration of nicotine with apomorphine for 14 days resulted in a decrease in the density of nerve terminal glutamate immunolabeling compared to the nicotine-treated group. Following subehronic treatment of 6-OHDA-lesioned rats with apomorphine for 7 or 14 days, there was an increase in the number of apomorphine-induced contralateral rotations compared to the saline treated group. There was a decrease in the number of apomorphine-induced contralateral rotations in the group coadministered nicotine with apomorphine for 7 or 14 days compared to the apomorphine treated group. The data suggests that in this 6-OHDA lesion model of Parkinson's disease, treatment with nicotine may be useful in counteracting the increased behavioral effect (i.e., contralateral rotations) observed after treatment with a dopamine agonist, such as apomorphine. (C) 2002 Elsevier Science (USA).