Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats
Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats
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DOI：
10.1126/science.281.5381.1349
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发表时间：
1998-08-28
期刊：
影响因子：
56.9
通讯作者：
Adams, BW
中科院分区：
文献类型：
--
作者：
Moghaddam, B;Adams, BW
谷氨酸能异常与几种精神疾病有关，包括精神分裂症和成瘾。II组代谢型谷氨酸受体的目标是正常化与精神分裂症的动物模型，苯环利定模型相关的谷氨酸能中断。这组受体的激动剂，在一个剂量，是没有影响自发活动和皮质边缘多巴胺神经传递，衰减苯环利定的破坏性影响的工作记忆，刻板，运动，和皮质谷氨酸流出。这种行为逆转发生在持续的多巴胺过度活跃的情况下。因此，靶向这组受体可能是治疗精神疾病的非多巴胺能治疗策略。
Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, Locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic: therapeutic strategy for treatment of psychiatric disorders.