Effects of pergolide treatment on in vivo hydroxyl free radical formation during infusion of 6-hydroxydopamine in rat striatum.
This study focused on the early neurochemical events involved in 6-hydroxydopamine (6-OHDA) neurotoxicity and the putative neuroprotective effects of pergolide. 6-OHDA in 0.1% ascorbic acid/saline was delivered into rat striatum by means of microdialysis and 2,3-dihydroxybenzoic acid (2,3-DHBA) was measured as an index of hydroxyl free radical formation using salicylate trapping. Infusion of 6-OHDA (2-20 mM) via the dialysis probe for 15 min was associated with an immediate and striking increase in the extracellular levels of 2,3-DHBA and dopamine, and this effect was dose-dependent. An infusion of 10 mM 6-OHDA, equivalent to a direct injection of approximately 4 microgram free base, resulted in dopamine overflow with a maximum approx. 200-fold above the baseline. This massive overflow of toxic amounts of dopamine, much greater than expected of reuptake inhibition, seems to be the earliest response of nigrostriatal neurones to 6-OHDA. In rats treated with pergolide mesylate (7 days 0.5 mg/kg/day, i.p.), the average amount of 2, 3-DHBA associated with 6-OHDA striatal infusion was significantly smaller than that in controls. This suggests that pergolide treatment leads to an increased ability of striatal tissue to quench hydroxyl radical formation in vivo.
Opacka-Juffry
J
J
Imperial College School of Medicine, Division of Neurosciences, MRC Cyclotron Unit, Hammersmith Hospital, London W12 OHS, UK.
Wilson
A W
AW
Blunt
S B
SB
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007267:Injections; D008297:Male; D017072:Neostriatum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D010479:Pergolide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology*
D000978:Antiparkinson Agents; D016166:Free Radical Scavengers; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D010479:Pergolide; D017665:Hydroxyl Radical; D016627:Oxidopamine; D004298:Dopamine