Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system
Stress-induced cross-sensitization to amphetamine is related to changes in the dopaminergic system
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DOI：
10.1007/s00702-011-0720-8
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发表时间：
2012-04-01
影响因子：
3.3
通讯作者：
Planeta, Cleopatra S.
中科院分区：
文献类型：
--
作者：
Cruz, Fabio C.;Marin, Marcelo Tadeu;Planeta, Cleopatra S.
反复的压力会导致行为敏感化。中脑边缘多巴胺系统在药物诱导的行为敏化中起关键作用。在本研究中，我们研究了青春期和成年大鼠之间的差异，在应激诱导的行为敏感安非他明和多巴胺（DA）及其代谢产物的水平在中脑边缘系统的变化。将青春期或成年大鼠束缚2 h，每日1次，连续7 d。在最后一次暴露于应激后三天，将动物用盐水或安非他明（1.0 mg/kg i. p.）行为学实验结束后，立即断头取下丘脑腹侧被盖区（VTA）、杏仁核（AM）和延髓背侧核（NAcc），用高效液相色谱法测定DA及其代谢产物的含量。暴露于反复约束压力促进行为敏感安非他明在成年和青少年大鼠。在成年大鼠中，安非他明管理增加DA水平的压力和控制组在NAcc和VTA。在青春期大鼠中，安非他明增加了暴露于压力的大鼠NAcc中的DA水平。此外，在对照组青春期大鼠的上午，安非他明增加了DA水平;然而，安非他明减少了暴露于压力的大鼠的这种神经递质。未观察到多巴胺代谢物水平的变化。因此，应激促进了对苯丙胺的行为敏感化，这可能与中脑边缘系统中DA水平的变化有关。这些变化似乎是依赖于个体发育。
Repeated stress engenders behavioral sensitization. The mesolimbic dopamine system is critically involved in drug-induced behavioral sensitization. In the present study we examined the differences between adolescent and adult rats in stress-induced behavioral sensitization to amphetamine and changes in dopamine (DA) and its metabolite levels in the mesolimbic system. Adolescent or adult rats were restrained for 2 h, once a day, for 7 days. Three days after the last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded for 40 min. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens (NAcc), ventral tegmental area (VTA) and amygdala (AM) were removed to measure tissue levels of DA and its metabolites by HPLC. Exposure to repeated restraint stress promoted behavioral sensitization to amphetamine in both adult and adolescent rats. In adult rats, amphetamine administration increased DA levels in both the stress and control groups in the NAcc and VTA. In adolescent rats, amphetamine increased DA levels in the NAcc in rats exposed to stress. Furthermore, in the AM of adolescent rats in the control group, amphetamine increased the DA levels; however, amphetamine reduced this neurotransmitter in the rats that were exposed to stress. No alteration was observed in the dopamine metabolite levels. Therefore, stress promoted behavioral sensitization to amphetamine and this may be related to changes in DA levels in the mesolimbic system. These changes appear to be dependent on ontogeny.