Blake Bonita L, Muehlmann Amber M, Egami Kiyoshi, Breese George R, Devine Darragh P, Jinnah H A
Department of Psychiatry, University of North Carolina, Chapel Hill, USA.
Dev Neurosci. 2007;29(3):241-50. doi: 10.1159/000096414. Epub 2006 Oct 17.
Self-injurious behavior is a common problem in many developmental disorders. The neurobiology of this behavior is not well understood, but the differing behavioral manifestations and associations with different disorders suggest that the underlying biological mechanisms are heterogeneous. The behavioral and biological heterogeneity is also evident in several animal models, where different manifestations can be provoked under different experimental conditions. Identifying commonalities among the different mechanisms is likely to be helpful in the design of treatments useful for the broadest populations of patients. The current studies reveal that nifedipine suppresses self-injurious behavior in 4 unrelated animal models: acute administration of high doses of +/-BayK 8644 or methamphetamine in mice, dopamine agonist treatment in rats with lesions of dopamine pathways during early development and repeated administration of pemoline in rats. The effect of nifedipine does not appear to be due to nonspecific mechanisms, such as sedation, since other classes of behaviors are unaffected or exaggerated. These results suggest that nifedipine may target a common biological mechanism in the expression of self-injurious behavior, and they suggest it should be considered in the treatment of self-injury in humans.
自伤行为是许多发育障碍中的常见问题。这种行为的神经生物学机制尚未得到充分理解,但不同的行为表现以及与不同障碍的关联表明,其潜在的生物学机制是异质性的。行为和生物学的异质性在几种动物模型中也很明显,在不同的实验条件下可以引发不同的表现。识别不同机制之间的共性可能有助于设计对最广泛患者群体有用的治疗方法。目前的研究表明,硝苯地平在4种不相关的动物模型中抑制自伤行为:给小鼠急性高剂量注射+/-BayK 8644或甲基苯丙胺、对早期发育期间多巴胺通路受损的大鼠进行多巴胺激动剂治疗以及对大鼠反复给予匹莫林。硝苯地平的作用似乎并非由于非特异性机制,如镇静作用,因为其他类型的行为未受影响或反而增强。这些结果表明,硝苯地平可能针对自伤行为表达中的一种常见生物学机制,并且表明在治疗人类自伤行为时应考虑使用它。