Department of Developmental Epileptology, Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic.
Pharmacol Biochem Behav. 2011 Oct;99(4):619-25. doi: 10.1016/j.pbb.2011.06.007. Epub 2011 Jun 15.
High doses of mGluR5 antagonists have anticonvulsant effects in multiple seizure models in both adult and immature animals. Data on potential behavioral effects in immature animals are very scarce. The present study investigated whether an antagonist of mGluR5 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) in doses proven to be anticonvulsant affects behavior in immature rats. Animals aged 12, 18 and 25 days received MTEP in doses of 20 and 40 mg/kg i. p. The sensorimotor performance was tested at 15 and 60 min after dosing. Locomotor-exploratory behavior was tested at 20 and 65 min after dosing. An elevated plus maze was used to examine an adaptive form of learning and anxiety-like behavior in 18- and 25-day-old rats at 15, 60 min and 24h. MTEP slightly affected sensorimotor performance, regardless of age. In the open field test, MTEP decreased transiently locomotor-exploratory behavior but did not affect the habituation - a simple form of nonassociative learning. In the elevated plus maze, the drug did not impair transfer latency, an indicator of an adaptive form of learning and memory. An anxiolytic-like effect was observed at 60 min after drug administration. In conclusion, no severe impairment was observed after high anticonvulsant doses of mGlu5 antagonist MTEP in immature animals.
高剂量的 mGluR5 拮抗剂在成年和未成年动物的多种癫痫模型中均具有抗惊厥作用。关于未成年动物潜在行为影响的数据非常有限。本研究调查了在已证明具有抗惊厥作用的剂量下,mGluR5 的拮抗剂 3-((2-甲基-1,3-噻唑-4-基)乙炔基)吡啶 (MTEP) 是否会影响未成年大鼠的行为。12、18 和 25 日龄的动物分别接受 20 和 40 mg/kg i.p. 的 MTEP 治疗。在给药后 15 和 60 分钟测试感觉运动表现。在给药后 20 和 65 分钟测试运动探索行为。高架十字迷宫用于在 18 和 25 日龄大鼠中在 15、60 分钟和 24 小时检查适应性学习和焦虑样行为。MTEP 轻微影响感觉运动表现,与年龄无关。在旷场试验中,MTEP 短暂地减少了运动探索行为,但不影响习惯化——一种简单的非联想学习形式。在高架十字迷宫中,药物不影响转移潜伏期,转移潜伏期是适应性学习和记忆的一种指标。给药后 60 分钟观察到抗焦虑样作用。总之,在未成年动物中,高剂量的 mGlu5 拮抗剂 MTEP 没有观察到严重的损伤。