Moghaddam B, Adams B W
Department of Psychiatry, Yale University School of Medicine, Veterans Administration Medical Center 116A/2, West Haven, CT 06516, USA.
Science. 1998 Aug 28;281(5381):1349-52. doi: 10.1126/science.281.5381.1349.
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.
谷氨酸能异常与包括精神分裂症和成瘾在内的多种精神疾病有关。Ⅱ型代谢型谷氨酸受体被作为靶点，以恢复与精神分裂症动物模型（苯环利定模型）相关的谷氨酸能紊乱。该组受体的一种激动剂，在对自发活动和皮质边缘多巴胺神经传递无影响的剂量下，减弱了苯环利定对工作记忆、刻板行为、运动及皮质谷氨酸外流的破坏作用。尽管多巴胺持续亢进，这种行为逆转仍会发生。因此，针对该组受体可能为精神疾病的治疗提供一种非多巴胺能治疗策略。
