Electrochemical investigation of dopamine neurotransmission involving iontophoresis Public Deposited

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  • March 20, 2019
  • Seipel, Andrew
    • Affiliation: College of Arts and Sciences, Department of Chemistry
  • Identification of the role of transient dopamine release in behavior has proved difficult. In order to interpret the complex processes involved in dopamine neurotransmission, dopamine release and cell firing rates must be recorded and the signals correlated through pharmacological manipulation. For this purpose, the carbon-fiber electrodes employed for electrochemical dopamine detection and extracellular unit recordings were combined with the local drug delivery technique, iontophoresis. The application of glutamate, dopamine, and the glutamate receptor antagonist, CNQX, by iontophoresis strongly modulated cell firing rates in anesthetized rats with short (20 s) ejections. The ejection of glutamate and the dopamine receptor agonist, quinpirole HCl, strongly decreased stimulated dopamine release though required ejections several minutes long. The stimulated dopamine release studies are believed to require greater distances the ejected compound must diffuse in order to generate a detectable effect. This increased distance may explain the drastic difference in ejection durations. Glutamate was found to increase firing in a minority of neurons and no observed effect from dopamine in freely-moving animals. However, long ejections of the D1 antogonist, SCH23390, inhibited cell firing during ICSS behavior. The amount of basal dopamine present in the extracellular fluid was also studied. Dopamine levels were monitored during microinjection of saline and lidocaine in the ventral tegmental area and systemic cocaine administration. With both impulse-dependent dopamine release and dopamine reverse transport blocked, minimal decreases in dopamine were observed (less than 25 nM) that are similar to levels obtained in recent microdialysis estimates. A novel action of cocaine was also investigated using genetically-modified mice. The effect of cocaine upon stimulated dopamine release in mice lacking all 3 isoforms of the protein, synapsin, was investigated using fast-scan cyclic voltammetry and amperommetry. Cocaine was found to increase dopamine release through not only decreasing uptake but through increasing the amount of dopamine released per stimulus event. During depleting (15 second) electrical stimulations and after synthesis inhibition via a-methyl-para-tyrosine administration, the synapsin TKO mice showed a decreased response to cocaine with respect to wild-type mice. This suggests an interaction between a synapsin-dependent pool of dopamine vesicles and cocaine.
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  • Wightman, R. Mark
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