In vivo evidence for a concordant response of terminal and dendritic dopamine release during intranigral infusion of drugs

In the present study we have administered prototypical drugs of 5 different receptors (D-2, GABA-A, GABA-B, NMDA, kainate) to the substantia nigra by infusion via a microdialysis probe, whereas the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were recorded both in the substantia nigra and (by a second microdialysis probe) in the ipsilateral striatum. Infusion of the specific D-2 receptor agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin ((-)N0437) into the nigra induced a decrease in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (after 10 mumol/l). During these infusions extracellular DOPAC decresed in the nigra and increased in the striatum. Infusion of the D-2 specific receptor antagonist (-)-sulpiride into the nigra induced an increase in the release of dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum (10 mumol/l). During these infusions a slight increase of extracellular DOPAC was noticed in the nigra. Infusion of the GABA-A receptor antagonist bicuculline into the nigra (50 mumol/l) induced an increase in the release of dopamine and DOPAC both in the nigra and ipsilateral striatum. Infusion of the GABA-B receptor agonist d,I-baclofen into the nigra (10 mumol/l) induced a decrease of in the release of dopamine in the nigra as well as in the ipsilateral striatum, whereas extracellular DOPAC decreased in the nigra and increased in the striatum. Infusion of the glutamate receptor agonist N-methyl-D-aspartate (NMDA) into the nigra induced an increase in the release of dopamine and DOPAC in the nigra (after 300 mumol/l) as well as in the ipsilateral striatum (after 1 mmol/l). Infusion of the glutamate receptor-agonist kainate into the nigra (10 mumol/l) induced an increase in the release of dopamine and DOPAC in the nigra as well as in the ipsilateral striatum. The results showed that nigral as well as striatal dopamine release respond in a concordant way to intranigral infusion of drugs.