Models of dopaminergic and serotonergic signaling

Pharmacopsychiatry. 2010 May:43 Suppl 1:S61-6. doi: 10.1055/s-0030-1252024. Epub 2010 May 17.

Abstract

Mathematical models of dopaminergic and serotonergic synapses have enabled the authors to study quantitative aspects of the synthesis, release and reuptake of dopamine and serotonin, to investigate the effects of autoreceptors, and to explore the influence of the neurochemistry on the firing patterns of cells known to be involved in the behavioral responses to dopaminergic and serotonergic signaling. The models consist of coupled ordinary differential equations. Parameters are determined from biochemical and physiological measurements. Three results from recent IN SILICO experiments with the dopaminergic and serotonergic synapse models are described: (1) influence of substrate inhibition on the stability of dopamine and serotonin synthesis; (2) a predicted connection between serotonin reuptake transporter (SERT) density on terminals and tonic firing rates; (3) an explanation of data from autoreceptor knock-out experiments. Mathematical models are useful for studying the biology of dopaminergic and serotonergic signaling because these systems are complex and involve interactions between neurochemistry and neurobiology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Computer Simulation
  • Dopamine / metabolism*
  • Extracellular Space / metabolism
  • Fluoxetine / pharmacology
  • Kinetics
  • Mice
  • Mice, Knockout
  • Models, Neurological*
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / physiology*
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptor, Serotonin, 5-HT1B / genetics
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Synapses / drug effects
  • Synapses / enzymology
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tryptophan Hydroxylase / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Receptor, Serotonin, 5-HT1B
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Tyrosine 3-Monooxygenase
  • Tryptophan Hydroxylase
  • Dopamine