Dopamine and 5-HT turnover are increased by the mGlu2/3 receptor agonist LY379268 in rat medial prefrontal cortex, nucleus accumbens and striatum
Dopamine and 5-HT turnover are increased by the mGlu2/3 receptor agonist LY379268 in rat medial prefrontal cortex, nucleus accumbens and striatum
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DOI：
10.1016/s0006-8993(00)03067-5
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发表时间：
2000-12-29
期刊：
影响因子：
2.9
通讯作者：
Schoepp, DD
中科院分区：
文献类型：
--
作者：
Cartmell, J;Salhoff, CR;Schoepp, DD
我们使用体内微透析采样显示，选择性II组代谢性(MGlu)受体激动剂LY379268，如非典型抗精神病药物氯氮平，可增加大鼠内侧前额叶皮质(MPFC)细胞外多巴胺、多巴胺代谢物DDPAC和HVA以及主要5-羟色胺代谢物5-HIAA的水平。在这里，我们比较了LY379268与氯氮平以及利培酮对多个脑区体外组织中多巴胺、DOPAC、HVA、5-羟色胺和5-HIAA水平的影响。LY379268给药后1~2小时，mPFC组织中DOPAC、HVA和5-HIAA水平呈剂量依赖性增加。LY379268(10 mg/kg S.C.)2 h时分别为基础水平的189%、245%和139%。这些作用在给药后4小时内被逆转。氯氮平(10 mg/kg皮下注射)和利培酮(1 mg/kg s.c.)多巴胺代谢产物的水平也有类似程度的增加，但对组织中5-HIAA的水平没有明显影响。LY379268(10 mg/kg S.C.)在伏隔核，DOPAC、HVA和5-HIAA的组织水平分别增加了基础水平的169、221和134%；在纹状体中，分别增加了基础水平的131、179和132%。这些数据表明，mGlu2/3受体的激活可以增加与非典型抗精神病药物作用有关的大脑区域中多巴胺和5-羟色胺的周转。(C)2000年爱思唯尔科学研究院。版权所有。
We have shown, using in vivo microdialysis sampling, that systemic administration of the selective group II metabotropic (mGlu) receptor agonist LY379268, like the atypical antipsychotic clozapine, increased extracellular levels of dopamine, dopamine metabolites DDPAC and HVA, and the major 5-HT metabolite 5-HIAA, in rat medial prefrontal cortex (mPFC). Here, we have compared the effects of LY379268 with clozapine as well as risperidone on ex vivo tissue levels of dopamine, DOPAC, HVA, 5-HT and 5-HIAA in multiple brain regions. One to two hours following administration of LY379268, mPFC tissue levels of DOPAC, HVA and 5-HIAA were increased in a dose-dependent manner. Increases evoked by LY379268 (10 mg/kg s.c.) at the 2 h point were 189, 245 and 139% of basal-levels, respectively. These effects were reversed within 4 h of administration. Clozapine (10 mg/kg s.c.) and risperidone (1 mg/kg s.c.) also increased levels of the dopamine metabolites to a similar extent but were without significant effect on tissue levels of 5-HIAA. LY379268 (10 mg/kg s.c.) also increased tissue levels of DOPAC, HVA and 5-HIAA by 169, 221 and 134% of basal levels in nucleus accumbens, respectively, and by 131, 179 and 132% of basal levels in striatum, respectively. These data show that activation of mGlu2/3 receptors can increase the turnover of dopamine and 5-HT in the areas of the brain implicated in the actions of atypical antipsychotics. (C) 2000 Elsevier Science BSI. All rights reserved.