Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Brain Res. 2011 Aug 8;1405:23-30. doi: 10.1016/j.brainres.2011.06.019. Epub 2011 Jun 17.
Centrally acting cannabinoids are well known for their ability to impair functions associated with both learning and memory but appreciation of the physiological mechanisms underlying these actions, particularly those that persist, remains incomplete. Our earlier studies have shown that song stereotypy is persistently reduced in male zebra finches that have been developmentally exposed to cannabinoids. In the present work, we examined the extent to which changes in neuronal morphology (dendritic spine densities and soma size) within brain regions associated with zebra finch vocal learning are affected by late-postnatal cannabinoid agonist exposure. We found that daily treatment with the cannabinoid agonist WIN55212-2 (WIN, 1mg/kg IM) is associated with 27% and 31% elevations in dendritic spine densities in the song regions Area X and HVC, respectively. We also found an overall increase in cell diameter within HVC. Changes in dendritic spine densities were only produced following developmental exposure; treatments given to adults that had completed vocal learning were not effective. These findings have important implications for understanding how repeated cannabinoid exposure can produce significant, lasting alteration of brain morphology, which may contribute to altered development and behavior.
中枢作用的大麻素因能够损害与学习和记忆相关的功能而广为人知，但对这些作用背后的生理机制的理解，尤其是那些持续存在的机制，仍不完整。我们之前的研究表明，在发育过程中接触大麻素的雄性斑马雀的刻板歌曲行为会持续减少。在目前的工作中，我们研究了在与斑马雀发声学习相关的脑区中，神经元形态（树突棘密度和胞体大小）的变化在多大程度上受到晚期大麻素激动剂暴露的影响。我们发现，每日给予大麻素激动剂 WIN55212-2（WIN，1mg/kg IM）治疗与 Area X 和 HVC 这两个与鸣禽发声学习相关的脑区中的树突棘密度分别增加了 27%和 31%。我们还发现 HVC 中的细胞直径总体增加。只有在发育过程中暴露于大麻素时才会产生树突棘密度的变化；给予已经完成发声学习的成年动物的治疗没有效果。这些发现对于理解重复接触大麻素如何产生对大脑形态的显著、持久的改变具有重要意义，这种改变可能导致发育和行为的改变。
