Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies.
In the present study in vivo and ex vivo experiments were combined to evaluate the effects of allopurinol on the neurochemical changes induced by an acute morphine challenge (2 mg kg-1, s.c.). In samples from rat striatum, levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), ascorbate (AA), dehydroascorbate (DHAA), hypoxanthine, xanthine and uric acid (UA) were measured. Brain microdialysis experiments were carried out in freely moving rats. Striatal dialysate levels were assayed for DA, DOPAC + HVA, AA and UA using liquid chromatography followed by electrochemical detection. Morphine administration increased the striatal levels of DA metabolites, UA and DHAA and the extracellular concentrations of DA, DOPAC + HVA, UA and AA. Allopurinol (50 mg kg-1 by gavage), an inhibitor of xanthine oxidase which catalyses oxidation of xanthine to UA, decreased basal UA and AA concentrations and the morphine-induced increase in DA metabolites and AA oxidation. Since oxidation of DA and xanthines generates reactive oxygen species (ROS) and AA and UA are the main cellular antioxidants, these findings suggest that: (a) single morphine administration increases DA and xanthine oxidative metabolism with a consequent increase in ROS production, which may account for changes in concentrations of extracellular AA and tissue DHAA; (b) allopurinol decreases morphine-induced DA and xanthine oxidation; (c) UA and AA may act in concert to regulate levels of ROS in the brain.
Enrico
P
P
Institute of Pharmacology, University of Sassari, Italy.
Esposito
G
G
Mura
M A
MA
Migheli
R
R
Serra
P A
PA
Desole
M S
MS
Miele
E
E
De Natale
G
G
Miele
M
M
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D014527:Uric Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014527:Uric Acid; D000493:Allopurinol; D009020:Morphine; D014969:Xanthine Oxidase; D001205:Ascorbic Acid; D004298:Dopamine