Acute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections
Acute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections
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DOI：
10.1046/j.1460-9568.2001.02009.x
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发表时间：
2002-06-01
影响因子：
3.4
通讯作者：
Zoli, M
中科院分区：
文献类型：
--
作者：
Ferrari, R;Le Novère, N;Zoli, M
在尼古丁处理的动物中，我们检测了与中脑边缘多巴胺(DA)通路功能有关的几个神经化学和行为参数，在三种给药模式下，即全身注射、伏隔(ACB)注射或腹侧被盖区(VTA)内微量注射。目前全身给药、ACB内给药和VTA内给药均可引起ACB透析液中DA水平的显著升高。在全身或VTA内注射尼古丁的习惯性环境中，细胞外DA水平的增加与运动的显著增强是平行的，而单侧或双侧ACB内注射尼古丁无效，表明在本实验范式中，累积区DA的增加不足以引起运动。在VTA内，但不是全身或ACB内，尼古丁给药导致ACB基础透析液DA水平的长期(至少24小时)增加。此外，在VTA内注射尼古丁24小时后，VTA内酪氨酸羟化酶(TH)和GluR1(但不包括多巴胺转运体或NR1)的mRNA水平显著升高。全身注射尼古丁仅引起TH mRNA水平的增加，而ACB内注射并不改变所测试的任何mRNAs。VTA内微量注射尼古丁后，ACB和TH的基础DA水平和VTA中GluR1mRNA水平的长期升高表明，即使是一次尼古丁注射也可以诱导中脑边缘DA通路的可塑性变化。
We have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra-accumbens (Acb) infusion or intraventral tegmental area (intra-VTA) microinjection. The present modes of systemic, intra-Acb and intra-VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra-VTA nicotine administration, whereas unilateral or bilateral intra-Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra-VTA, but not systemic or intra-Acb, nicotine administration caused a long-term (at least 24-h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra-VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra-Acb infusion did not modify any of the mRNAs tested. The long-term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra-VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway.