Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo.
Constant potential amperometry (CPA) was used for in vivo recording of extracellular dopamine (DA) after electrical stimulation of the medial forebrain bundle (MFB) (4 pulses, 2 mA, 20 or 100 Hz) in the striatum of the rat brain. CPA signals were analysed in the absence and presence of the DA uptake inhibitor nomifensine with the help of a mathematical model which considered both the influence of DA diffusion after its stimulated release and the Michaelis-Menten kinetics of cellular DA uptake from the extracellular space. We found an excellent conformity of experimentally obtained CPA signals and calculated curves. Mathematical analysis revealed that CPA signals were strongly influenced by DA diffusion. The kinetic parameters calculated from CPA signals in this study were in agreement with experimental determinations of Vmax and Km of extracellular DA uptake in other studies and reflect the particular pharmacological properties of nomifensine. CPA is a useful and efficient method for in vivo estimation of individual changes of DA kinetic parameters by pharmacological treatment.
Schönfuss
D
D
Institute of Pharmacology and Toxicology, Medical Faculty (Charité) of the Humboldt University at Berlin, Dorotheenstrasse 94, D-10117, Berlin, Germany.
Reum
T
T
Olshausen
P
P
Fischer
T
T
Morgenstern
R
R
D000818:Animals; D002244:Carbon; D000077482:Carbon Fiber; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004566:Electrodes / Q000592:standards*; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D008959:Models, Neurological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000077482:Carbon Fiber; D018765:Dopamine Uptake Inhibitors; D009627:Nomifensine; D002244:Carbon; D004298:Dopamine