Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec, H4H 1R3, Canada.
Behav Brain Res. 2012 Apr 1;229(1):202-7. doi: 10.1016/j.bbr.2012.01.008. Epub 2012 Jan 13.
The guidance cue netrin-1 acting on mesocorticolimbic dopamine (DA) neurons through its receptor DCC (deleted in colorectal cancer) has been implicated in the neuronal plasticity induced by psychostimulant drugs. We examined in C57/BL6 mice the effects of repeated juvenile methylphenidate (MPH) exposure on cocaine-reward sensitivity in adulthood and determined whether early MPH treatment alters adult expression of DCC in mesocorticolimbic DA regions. By using place conditioning, we show that adult mice exposed to MPH during the juvenile period are less sensitive to cocaine-reward compared to saline-controls. Furthermore, by means of immunoblotting, we demonstrate that early MPH treatment attenuates adult DCC expression in the ventral tegmental area (VTA) selectively. These results support previous evidence that developmental MPH treatment diminishes cocaine-reward in adulthood and are the first to suggest that DCC in the VTA may participate in this enduring effect.
神经导向因子 netrin-1 通过其受体 DCC（结直肠癌缺失）作用于中脑皮质边缘多巴胺（DA）神经元，与精神兴奋剂诱导的神经元可塑性有关。我们在 C57/BL6 小鼠中研究了幼年时反复接触哌甲酯（MPH）对成年可卡因奖赏敏感性的影响，并确定早期 MPH 治疗是否改变成年中脑皮质边缘 DA 区的 DCC 表达。通过位置条件作用，我们发现，与生理盐水对照组相比，在幼年时期接受 MPH 暴露的成年小鼠对可卡因奖赏的敏感性降低。此外，通过免疫印迹，我们证明早期 MPH 治疗选择性地减弱了腹侧被盖区（VTA）中的成年 DCC 表达。这些结果支持了先前的证据，即发育性 MPH 治疗可降低成年期可卡因的奖赏作用，并且首次表明 VTA 中的 DCC 可能参与这种持久的效应。
