Extracellular dopamine in striatum: Influence of nerve impulse activity in medial forebrain bundle and local glutamatergic input

K. A. Keefe, M. J. Zigmond, E. D. Abercrombie

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126 Scopus citations

Abstract

Microdialysis probes were used to measure dopamine in, and to administer glutamate receptor antagonists and agonists to, the striatum of unanesthetized rats. Antagonists used were: kynurenate, 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. Agonists used were: N-methyl-d-aspartate and kainate. In some rats an additional dialysis probe was implanted in medial forebrain bundle for infusion of tetrodotoxin (10μM) to block action potential propagation along dopaminergic axons in this pathway. The latter treatment reduced dopamine in striatal dialysate to below detectable levels (<0.5 pg). The quantity of dopamine in striatal dialysate was not reduced by the local application of glutamate receptor antagonists. At lower concentrations, the receptor antagonists failed to alter significantly the quantity of dopamine, whereas the highest concentration of each antagonist increased the amount of dopamine in the dialysate. At the highest concentration tested (0.75 mM or 1.0 mM), as well as at a lower concentration (0.1 mM), 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione blocked the dopamine-releasing effects of exogenously applied N-methyl-d-aspartate (1.0 mM) or kainate (0.1 mM), respectively. Thus, concentrations of glutamate receptor antagonists that produced effective pharmacological blockade of the respective receptors had no effect on the basal amount of dopamine in striatal extracellular fluid. Finally, N-methyl-d-aspartate and kainate produced a significant elevation in extracellular dopamine during the infusion of tetrodotoxin into the medial forebrain bundle, indicating that impulse activity in this pathway is not necessary for dopamine release produced by glutamate receptor agonists. We conclude that the basal amount of dopamine in striatal dialysate in unanesthetized rats during quiet waking or sleep is determined by the electrophysiological activity of nigrostriatal dopamine neurons. Despite numerous reports that glutamate receptor agonists are able to stimulate dopamine release in striatum, the present data obtained using glutamate receptor antagonists suggest that endogenous glutamate exerts no tonic effect on extracellular dopamine in striatum under these conditions.

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalNeuroscience
Volume47
Issue number2
DOIs
StatePublished - Mar 1992

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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