化学
乙酰胆碱酯酶
乙酰胆碱酯酶抑制剂
色谱法
药理学
多巴胺
毒蕈碱乙酰胆碱受体
乙酰胆碱
液相色谱-质谱法
丁酰胆碱酯酶
胆碱酯酶
多巴胺受体D2
串联质谱法
选择性反应监测
乙酰胆碱受体
作者
Laurent Lacroix,Laura Ceolin,Alessandro Zocchi,Giorgia Varnier,Marco Garzotti,Ornella Curcuruto,Christian Heidbreder
标识
DOI:10.1016/j.jneumeth.2006.03.017
摘要
Abstract The present study compared the effects of two selective dopamine (DA) D 3 receptor antagonists, SB-277011A (3, 10 and 30 mg/kg i.p.) and SB-414796A (3, 10 and 30 mg/kg i.p.) on extracellular levels of acetylcholine (ACh) in the rat medial prefrontal cortex (mPFC) by using a LC/MS–MS analytical method that permitted the detection of ACh without the necessity of adding acetylcholinesterase inhibitors to the perfusate. Furthermore, the present LC/MS–MS method permitted the simultaneous measurement of the respective concentrations of SB-277011A and SB-414796A in the same extracellular samples from the mPFC. The systemic administration of both selective DA D 3 receptor antagonists produced a significant increase in extracellular levels of Ach compared to vehicle-treated animals, which was associated with increases in extracellular concentrations of SB-277011A and SB-414796. Overall, the present findings further strengthen the likelihood of a modulation of cortical cholinergic function through a DA D 3 -mediated mechanism and suggest that selective DA D 3 receptor antagonism may be beneficial in the treatment of psychiatric diseases, such as schizophrenia, which are characterized by cognitive dysfunction.
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