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Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies

Enrico, Paolo and Esposito, Giovanni and Mura, Maria A. and Migheli, Rossana and Serra, Pier Andrea and Desole, Maria Speranza and Miele, Egidio and De Natale, Guglielmo and Miele, Maddalena (1997) Effects of allopurinol on striatal dopamine, ascorbate and uric acid during an acute morphine challenge: ex vivo and in vivo studies. Pharmacological Research, Vol. 35 (6), p. 577-585. ISSN 1043-6618. Article.

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DOI: 10.1006/phrs.1997.0193

Abstract

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.

Item Type:Article
ID Code:4374
Status:Published
Refereed:Yes
Uncontrolled Keywords:Morphine, allopurinol, striatal dopamine, uric acid, ascorbate
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
001 Università di Sassari > 01 Dipartimenti > Neuroscienze, scienze materno infantili
Publisher:Academic Press / Elsevier
ISSN:1043-6618
Copyright Holders:
Publisher Policy:© 1997 The Italian Pharmacological Society
Deposited On:26 Aug 2010 13:52

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