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 decreased 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
B H
BH
Westerink
M
M
Santiago
J B
JB
De Vries
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D015259:Dopamine Agents; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015102:3,4-Dihydroxyphenylacetic Acid; D013469:Sulpiride; C047508:rotigotine; D004298:Dopamine; D001640:Bicuculline