Transport mechanisms governing serotonin clearance in vivo revealed by high-speed chronoamperometry

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• 作者：Daws ; Lynette C. ; Monta脙脙ez ; Sylvia ; Owens ; W. Anthony ; Gould ; Georgianna G. ; Frazer ; Alan ; et. al.
• 关键词：Serotonin transporter ; Norepinephrine transporter ; Chronoamperometry ; Serotonin clearance rates ; Hippocampus ; Dorsal raphe nucleus ; Rat
• 刊名：Journal of Neuroscience Methods
• 出版年：2005
• 期刊代码：33_01650270
• 类别：neu
• 出版时间：April 15, 2005
• 卷：143
• 期：1
• 页码：49-62
• 文件大小：416 K

摘要

High-speed chronoamperometry was used to determine the kinetics of clearance of exogenously applied serotonin (5-HT) in the dorsal raphe nucleus (DRN), dentate gyrus, CA3 region of the hippocampus or corpus callosum of anesthetized rats. Maximal velocity (V_max) for 5-HT clearance was greatest in the DRN > dentate gyrus > CA3 > corpus callosum. Apparent affinity (K_T) of the serotonin transporter (5-HTT) was similar in DRN and CA3 but greater in dentate gyrus and corpus callosum. A 90%loss of norepinephrine transporters (NET) produced by 6-hydroxydopamine pretreatment, resulted in a two-fold reduction in V_max and a 30%decrease in K_T in the dentate gyrus, but no change in kinetic parameters in the CA3 region. Pretreatment with 5,7-dihydroxytryptamine that resulted in a 90%reduction in 5-HTT density, modestly reduced V_max in dentate gyrus but not in CA3. The same treatment had no effect on K_T in the dentate gyrus but increased K_T two-fold in the CA3. Neurotoxin treatments had no effect on 5-HT clearance in the corpus callosum. In hippocampal regions of intact rats, local application of the selective serotonin reuptake inhibitor, fluvoxamine, inhibited 5-HT clearance most robustly when the extracellular concentration of 5-HT was less than the K_T value. By contrast, the NET antagonist, desipramine, significantly inhibited 5-HT clearance when extracellular concentrations of 5-HT were greater than the K_T value. These data indicate that hippocampal uptake of 5-HT may be mediated by two processes, one with high affinity but low capacity (i.e. the 5-HTT) and the other with low affinity but a high capacity (i.e. the NET). These data show for the first time in the whole animal that 5-HT clearance in brain is regionally distinct with regard to rate and affinity.