期刊
JOURNAL OF NEUROSCIENCE METHODS
卷 121, 期 1, 页码 41-52出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-0270(02)00229-7
关键词
chronoamperometry; dopamine transporter; freely-moving rats; clearance; striatum; nomifensine; behavior; locomotor activity
资金
- NIA NIH HHS [AG06434] Funding Source: Medline
- NIDA NIH HHS [DA04216, DA00174] Funding Source: Medline
- NIMH NIH HHS [MH01245] Funding Source: Medline
- NINDS NIH HHS [NS39787] Funding Source: Medline
Previously, we developed technology that coupled high-speed chronoamperometry with microejections of dopamine (DA) to measure DA clearance in the brains of freely-behaving rats. Here, by varying the ejection volumes of DA across a 200-fold difference, the kinetics of striatal clearance were analyzed as a function of time and DA volume from 289 chronoamperometric signals (n = 20 rats). Each DA- clearance trace was fitted to a first-order exponential decay function to determine the rate constant for DA clearance (k). Additionally, the apparent Michaelis-Menten V-max and K-m kinetic constants were determined in freely-moving rats, enabling quantitative comparison of our values with other models of reuptake. The first-order rate constant for DA clearance, which reflects the V-max/K-m ratio or clearance efficiency, did not vary significantly when small volumes of DA were ejected resulting in peak DA signal amplitudes (A(max)) of < 5 μM. However, following nomifensine-induced DAT inhibition, A(max) was increased and k was attenuated simultaneously with behavioral activation; and A(max) and behavior remained elevated beyond the initial period. Our results indicate that the analysis of kinetic parameters from chronoamperometric DA signals may be useful for investigating drug-induced regulation of DAT kinetics in relation to the behavior of freely-moving rats. (C) 2002 Elsevier Science B.V. All rights reserved.
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