The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization
The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization
复制标题
脑源性神经营养因子在3,4-亚甲二氧基甲基苯丙胺诱导的位置偏好和行为敏化中的参与
DOI：
10.1016/j.bbr.2017.04.052
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
Toshitaka Nabeshima
中科院分区：
文献类型：
--
作者：
Akihiro Mouri;Yukihiro Noda;Minae Niwa;Yurie Matsumoto;Takayoshi Mamiya;Atsumi Nitta;Kiyofumi Yamada;Shoei Furukawa;Tatsunori Iwamura;Toshitaka Nabeshima
已知3，4-亚甲二氧基甲基苯丙胺（MDMA）可诱导人类产生依赖性和精神病。脑源性神经营养因子（BDNF）参与中脑多巴胺能神经元的突触可塑性和神经营养。本研究旨在探讨BDNF在MDMA依赖性和精神病中的作用。单剂量MDMA（10 mg/kg）诱导前额叶皮层、杏仁核和杏仁核中BDNF mRNA表达，但纹状体或海马中没有。然而，重复MDMA给药7天诱导纹状体和海马中BDNF mRNA的表达。前体和成熟BDNF蛋白表达在延髓核中增加，主要是在神经元中。此外，在重复给予MDMA后，在小鼠延髓核内观察到细胞外5-羟色胺水平迅速升高，细胞外多巴胺水平逐渐适度升高。多巴胺受体拮抗剂减弱重复MDMA给药对中脑核BDNF mRNA表达的影响。为了研究内源性BDNF在MDMA的行为和神经化学效应中的作用，我们使用了BDNF基因杂合缺失的小鼠。MDMA诱导的位置偏好，行为敏化，并在细胞外的5-羟色胺和多巴胺的水平增加，在BDNF杂合子敲除小鼠减弱。这些结果表明，BDNF参与MDMA诱导的依赖性和精神病通过激活中脑多巴胺能和多巴胺能神经元。
3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10 mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus. Both precursor and mature BDNF protein expression increased in the nucleus accumbens, mainly in the neurons. Additionally, rapidly increased extracellular serotonin levels and gradually and modestly increased extracellular dopamine levels were noted within the nucleus accumbens of mice after repeated MDMA administration. Dopamine receptor antagonists attenuated the effect of repeated MDMA administration on BDNF mRNA expression in the nucleus accumbens. To examine the role of endogenous BDNF in the behavioral and neurochemical effects of MDMA, we used mice with heterozygous deletions of the BDNF gene. MDMA-induced place preference, behavioral sensitization, and an increase in the levels of extracellular serotonin and dopamine within the nucleus accumbens, were attenuated in BDNF heterozygous knockout mice. These results suggest that BDNF is implicated in MDMA-induced dependence and psychosis by activating the midbrain serotonergic and dopaminergic neurons.