Jinnah H A, Yitta S, Drew T, Kim B S, Visser J E, Rothstein J D
Department of Neurology, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15228-32. doi: 10.1073/pnas.96.26.15228.
The L type calcium channel agonist (+/-)Bay K 8644 has been reported to cause characteristic motor abnormalities in adult mice. The current study shows that administration of this drug can also cause the unusual phenomenon of self-injurious biting, particularly when given to young mice. Self-biting is provoked by injecting small quantities of (+/-)Bay K 8644 directly into the lateral ventricle of the brain, suggesting a central effect of the drug. Similar behaviors can be provoked by administration of another L type calcium channel agonist, FPL 64176. The self-biting provoked by (+/-)Bay K 8644 can be inhibited by pretreating the mice with dihydropyridine L type calcium channel antagonists such as nifedipine, nimodipine, or nitrendipine. However, self-biting is not inhibited by nondihydropyridine antagonists including diltiazem, flunarizine, or verapamil. The known actions of (+/-)Bay K 8644 as an L type calcium channel agonist, the reproduction of similar behavior with another L type calcium channel agonist, and the protection afforded by certain L type calcium channel antagonists implicate calcium channels in the mediation of the self-biting behavior. This phenomenon provides a model for studying the neurobiology of this unusual behavior.
据报道，L型钙通道激动剂（±）Bay K 8644可在成年小鼠中引起特征性运动异常。当前研究表明，给予这种药物还会导致自伤性啃咬这一异常现象，尤其是在给予幼鼠时。将少量（±）Bay K 8644直接注入脑侧脑室可引发自咬行为，这表明该药物具有中枢效应。给予另一种L型钙通道激动剂FPL 64176也可引发类似行为。用二氢吡啶类L型钙通道拮抗剂（如硝苯地平、尼莫地平或尼群地平）预处理小鼠，可抑制（±）Bay K 8644引发的自咬行为。然而，包括地尔硫䓬、氟桂利嗪或维拉帕米在内的非二氢吡啶类拮抗剂并不能抑制自咬行为。（±）Bay K 8644作为L型钙通道激动剂的已知作用、另一种L型钙通道激动剂可重现类似行为以及某些L型钙通道拮抗剂提供的保护作用，表明钙通道参与了自咬行为的介导。这一现象为研究这种异常行为的神经生物学提供了一个模型。
