期刊
JOURNAL OF NEUROSCIENCE METHODS
卷 157, 期 1, 页码 25-31出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2006.03.017
关键词
acetylcholine; dopamine D-3 receptors; medial prefrontal cortex; microdialysis; SB-27701IA; SB-414796A
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 (110 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. (c) 2006 Elsevier B.V. All rights reserved.
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