Research paper
Modeling the dopaminergic nerve terminal

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Abstract

A method is described for developing and evaluating models of neurochemical processes. Computer simulation and simplex optimization are used to examine a model of the dopaminergic nerve terminal of the rat striatum. In the model, synthesis, storage, release, uptake, and metabolism are described by a set of non-linear differential equations. Parameters of the model are optimized with respect to diverse experimental data. These data include steady state passage of radioactivity, decline in total dopamine after synthesis inhibition, and change in extracellular dopamine concentration during electrical stimulation.

References (37)

  • H.F. Bradford

    Chemical Neurobiology

    (1985)
  • B.B. Brodie et al.

    Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines

    J. Pharmacol. Exp. Ther.

    (1966)
  • E. Costa et al.

    Compartmentation of striatal dopamine: problems in assessing the dynamics of functional and storage pools of transmitters

  • C.D. De Langen et al.

    Compartmental analysis of the accumulation of 3H-dopamine in synaptosomes from rat corpus striatum

    Naunyn-Schmiedeberg's Arch. Pharmacol.

    (1979)
  • J. Dedek et al.

    Turnover of free and conjugated (sulphonyloxy) dihydroxyphenylacetic acid and homovanillic acid in rat striatum

    J. Neurochem.

    (1979)
  • S.N. Deming et al.

    Simplex optimization of variables in analytical chemistry

    Anal. Chem.

    (1973)
  • M. Doteuchi et al.

    Compartmentation of dopamine in rat striatum

    Mol. Pharmacol.

    (1974)
  • A.G. Ewing et al.

    Two striatal compartments in the rat

    Science

    (1983)
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