期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1992
卷号：89
期号：12
页码：5591-5595
DOI：10.1073/pnas.89.12.5591
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The major mechanism underlying the neuroleptic action of the tridecapeptide neurotensin (NT) appears to be an interaction with dopamine receptor mechanisms based on biochemical binding and behavioral experiments. In vivo microdialysis was used in conscious rats to investigate the effects of local perfusion with NT on the sensitivity of striatal dopamine D1 and D2 receptors for their selective agonists by monitoring extracellular dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and gamma-aminobutyric acid levels in the awake unrestrained male rat. Perfusion with NT (10 nM) counteracted the inhibitory effects of the dopamine D2 agonist pergolide (500 nM) on extracellular levels of dopamine and gamma-aminobutyric acid. In contrast, NT (10 mM) significantly enhanced the reduction of extracellular striatal levels of dopamine after perfusion with the D1 agonist SKF 38393 (5 microM), and this combined treatment also resulted in a significant increase in the extracellular striatal levels of gamma-aminobutyric acid. These results provide in vivo evidence that NT regulates central dopamine transmission by reducing pre-and postsynaptic dopamine D2 and enhancing D1 receptor sensitivity possibly through an antagonistic NT receptor-D2 receptor interaction. This heteroregulation has the potential to substantially increase the plasticity within the dopamine synapse.
