The Regulatory Effects of Dopamine D1 Receptors in the Ventral Tegmental Area on the Mesocorticolimbic Dopaminergic System

• Main Authors: Pey-Ling Liu, 劉珮玲
• Other Authors: Wynn H. T. Pan
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/02909662862527635698

碩士 === 國立陽明大學 === 藥理學研究所 === 91 === The study was designed to investigate the regulatory effects of dopamine (DA) D1 receptors in the ventral tegmental area (VTA) on terminal DA release in the mesocorticolimbic dopaminergic system by in vivo microdialysis in chloral-hydrate anaesthetized rats. Intrategmental infusion of D1 receptor antagonist SCH-23390 10-8 M, 10-6 M and 10-4 M decreased extracellular glutamate (91.62.7 %, 86.72.3%, 72.73.3 %, respectively) in the VTA and dopamine levels in the NAC (87.52.9 %, 75.62.7 %, 65.14.8 %, respective) and mPFC (79.63.6 %, 74.35.2 %, 61.85.2%, respectively). Intrategmental infusion of D1 receptor agonist SKF-82958 10-6 M, 10-5 M and 10-4 M decreased extracellular glutamate (89.31.4 %, 84.02.5%, 72.55.2 %, respectively) in the VTA and dopamine levels in the NAC (90.82.9 %, 86.43.2 %, 77.44.0 %, respective) and mPFC (92.01.9 %, 78.33.6 %, 59.13.7 %, respectively). These results indicated that the changes of glutamate in the VTA was parallel to the dopamine changes in the terminal regions during intrategmental of SCH23390 or SKF-82958 infusion. To mimic the condition of glutamete decrease, we intrategmentally infused nonselective glutamate receptor antagonist kynurenic acid 1mM. We found that kynurenic acid decreased extracellular DA in the NAC (72.43.8 %) and mPFC (56.53.4 %). This result was similar to the effect of whether intrategmental infusion of D1 receptor antagonist or agonist caused glutamate levels decreased and then terminal dopamine release decreased. Taken together, we hypothesize that terminal DA level is regulated by D1 receptors through glutamate transmission in the VTA.