Kasahara Yoshiyuki, Sakakibara Yasufumi, Hiratsuka Takashi, Moriya Yuki, Lesch Klaus-Peter, Hall F Scott, Uhl George R, Sora Ichiro
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Advanced Interdisciplinary Biomedical Engineering, Tohoku University Graduate School of Medicine, Sendai, Japan.
Neuropsychopharmacol Rep. 2019 Jun;39(2):130-133. doi: 10.1002/npr2.12049. Epub 2019 Feb 4.
Repeated psychostimulant drug treatment, including methamphetamine, in rodents readily produces behavioral sensitization, which reflects altered brain function caused by repeated drug exposure. Dendritic remodeling of medium spiny neurons in the nucleus accumbens is thought to be an essential mechanism underlying behavioral sensitization. We recently showed that chronic methamphetamine treatment did not produce behavioral sensitization in serotonin transporter knockout mice.
In this study, we report the spine density of medium spiny neurons in the nucleus accumbens after repeated methamphetamine injection to examine morphological alterations in serotonin transporter knockout mice.
Golgi-COX staining clearly showed that the spine density of medium spiny neurons in the nucleus accumbens increased following repeated methamphetamine treatment in both wild-type and serotonin transporter knockout mice.
Our results suggested that augmented serotonergic neurotransmission produced by serotonin transporter deletion prevents the development of behavioral sensitization in a manner that is independent of dendritic remodeling in the nucleus accumbens.
在啮齿动物中,包括甲基苯丙胺在内的反复精神刺激药物治疗很容易产生行为敏化,这反映了反复接触药物引起的大脑功能改变。伏隔核中中等棘状神经元的树突重塑被认为是行为敏化的一个重要机制。我们最近发现,慢性甲基苯丙胺治疗在血清素转运体基因敲除小鼠中不会产生行为敏化。
在本研究中,我们报告了反复注射甲基苯丙胺后伏隔核中中等棘状神经元的棘密度,以检查血清素转运体基因敲除小鼠的形态学改变。
高尔基-考克斯染色清楚地表明,在野生型和血清素转运体基因敲除小鼠中,反复给予甲基苯丙胺治疗后,伏隔核中中等棘状神经元的棘密度均增加。
我们的结果表明,血清素转运体缺失所产生的增强的血清素能神经传递以一种独立于伏隔核树突重塑的方式阻止了行为敏化的发展。