Characterization and pharmacological responsiveness of dopamine release recorded by microdialysis in the substantia nigra of conscious rats.
The extracellular concentration of dopamine (DA) and 3,4-dihydroxyphenylacetic acid in the substantia nigra (SN) and striatum was estimated by microdialysis. The dialysate content of DA from the SN was recorded during infusion of a DA uptake blocker (nomifensine; 5 mumol/L) dissolved in the perfusion fluid. Perfusion of tetrodotoxin (1 mumol/L) produced a virtually complete disappearance of nigral and striatal DA release. Dendritic as well as terminal release of DA was inhibited for several hours when the nerve impulse flow in dopaminergic neurons was blocked by systemic administration of gamma-butyrolactone (750 mg/kg, i.p.). The systemic administration (0.3 mg/kg, i.p.) as well as infusion (1 mumol/L) of the D2 agonist (-)-N-0437 [2-(n-propyl-N-2-thienylethylamino)-5-hydroxytetralin] produced a significant decrease in the release of DA in both the striatum and the SN. DA levels were recorded in the striatum both with and without addition of nomifensine to the perfusion fluid. The decrease in the striatum after (-)-N-0437 was suppressed in the presence of nomifensine. Infusion (1 mumol/L) as well as systemic administration (40 mg/kg) of sulpiride caused a similar increase in the release of striatal DA; this increase was, in both experiments, potentiated by nomifensine coinfusion. Sulpiride administration induced a small increase in the release of nigral DA. Infusion of (-)-N-0437 or (-)-sulpiride into the nigra caused a moderate decrease and increase, respectively, of striatal DA level.(ABSTRACT TRUNCATED AT 250 WORDS)
University Centre for Pharmacy, Department of Medicinal Chemistry, University of Groningen, The Netherlands.
M
M
Santiago
B H
BH
Westerink
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015107:4-Butyrolactone / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003243:Consciousness; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008832:Microchemistry; D009627:Nomifensine / Q000008:administration & dosage / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D013779:Tetrodotoxin; D013469:Sulpiride; C047508:rotigotine; D015107:4-Butyrolactone; D004298:Dopamine