Department of Pharmacology, School of Medicine, University of Thessaly, Mezourlo, P.O. Box 1400, 411-10 Larissa, Greece.
Eur J Pharmacol. 2013 Sep 5;715(1-3):105-10. doi: 10.1016/j.ejphar.2013.05.048. Epub 2013 Jun 11.
The activation of Group II metabotropic glutamate 2/3 (mGlu2/3) receptors reduces the excessive glutamate release that is hypothesized to be associated with neurodegenerative and psychiatric disorders. LY379268 is a highly potent mGlu2/3 receptor agonist that has shown efficacy in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. The present study investigated the effects of LY379268 on anxiety-like behavior in rats assessed in the light/dark and open field tests. The effects of LY379268 on motility in a locomotor activity chamber were also investigated in rats. Administration of the two lower doses of LY379268 used (0.3 and 1mg/kg) did not influence rats' performance either in the light/dark or in the open field test. Importantly, the administration of a higher LY379268 dose (3mg/kg) induced decrease in the number of transitions between the light and dark chambers and time spent in the light chamber compared to the vehicle-treated animals in the light/dark test. In the open field test, rats that received 3mg/kg LY379268 made fewer entries and spent less time in the central zone of the apparatus, exhibited a decrease of rearing episodes, but displayed higher grooming activity compared to controls. Nevertheless, the 3mg/kg dose did not alter locomotor activity compared with vehicle-treated rats in a motility test. The present results indicate that the highest LY379268 dose used in this study induced an anxiety-like effect in the light/dark and open field tests that cannot be attributed to changes in locomotor activity, while lower doses had no effect.
Group II 代谢型谷氨酸 2/3(mGlu2/3) 受体的激活可减少过度的谷氨酸释放，这种释放被认为与神经退行性和精神疾病有关。LY379268 是一种高效的 mGlu2/3 受体激动剂，已在几种中风、癫痫、药物滥用、精神分裂症和疼痛的动物模型中显示出疗效。本研究探讨了 LY379268 对大鼠在明暗和旷场测试中焦虑样行为的影响。还研究了 LY379268 对大鼠在运动活动室中的运动的影响。使用的两种较低剂量的 LY379268（0.3 和 1mg/kg）给药均未影响大鼠在明暗或旷场测试中的表现。重要的是，与接受载体处理的动物相比，较高剂量的 LY379268（3mg/kg）给药可减少动物在明暗测试中从亮室到暗室的转换次数和在亮室中花费的时间。在旷场测试中，接受 3mg/kg LY379268 的大鼠进入中央区域的次数减少，在中央区域的时间减少，表现出后肢站立次数减少，但与对照组相比，梳理行为增加。然而，与接受载体处理的大鼠相比，3mg/kg 剂量在运动性测试中并未改变运动活性。本研究结果表明，在所研究的最高 LY379268 剂量下，在明暗和旷场测试中引起了焦虑样效应，这不能归因于运动活性的变化，而较低剂量则没有影响。
