title: Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric acid release in freely moving rats.
abstract: Recent findings have shown that systemic morphine increases extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), ascorbic acid (AA) and uric acid concentrations in the striatum of freely moving rats. The morphine-induced increase in DA oxidative metabolism is highly correlated with that of xanthine. In the present study, we evaluated the effects of subcutaneous (s.c.) naloxone (1 mg/kg) on morphine-induced changes in DA, DOPAC, HVA, 5-hydroxyindoleacetic acid (5-HIAA), AA, uric acid and glutamate in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection or (glutamate) ultraviolet detection. Morphine (5-20 mg/kg) given s.c. increased DA, DOPAC+HVA, 5-HIAA, AA and uric acid and decreased glutamate dialysate concentrations over a 3 h period after morphine. Morphine (1 mM), given intrastriatally, did not affect all the above parameters, with the exception of an early short-lasting decrease in AA concentration. Naloxone antagonised all morphine-induced changes with the exception of AA increase and glutamate decrease in dialysate concentrations. Systemic or intrastrial (0.2-2 mM) naloxone increased AA and decreased glutamate dialysate concentrations. When given intranigrally, morphine (1 mM) increased DOPAC+HVA, AA and uric acid and decreased glutamate dialysate concentrations over a 2 h period after morphine; DA and 5-HIAA concentrations were unaffected. These results suggest that: (i) morphine increases striatal DA release and 5-hydroxytryptamine oxidative metabolism by a micro-opioid receptor-mediated mechanism mainly at extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative metabolism and affects glutamate and AA release by a micro-opioid receptor mediated mechanism acting also at nigral sites; and (iii) a micro-opioid receptor-mediated mechanism tonically controls at striatal sites extracellular AA and glutamate concentrations.
authors.affiliation: Institute of Pharmacology, University of Sassari, Viale S. Pietro 43/B, 07100 Sassari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Enrico
authors.forename: M A
authors.initials: MA
authors.lastname: Mura
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: P
authors.initials: P
authors.lastname: Serra
authors.forename: R
authors.initials: R
authors.lastname: Migheli
authors.forename: G
authors.initials: G
authors.lastname: De Natale
authors.forename: M S
authors.initials: MS
authors.lastname: Desole
authors.forename: M
authors.initials: M
authors.lastname: Miele
authors.forename: E
authors.initials: E
authors.lastname: Miele
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D014527:Uric Acid; D009270:Naloxone; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D009020:Morphine; D001205:Ascorbic Acid; D004298:Dopamine; D006719:Homovanillic Acid