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Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric acid release in freely moving rats

Enrico, Paolo and Mura, Maria A. and Esposito, Giovanni and Serra, Pier Andrea and Migheli, Rossana and De Natale, Guglielmo and Desole, Maria Speranza and Miele, Maddalena and Miele, Egidio (1998) Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric acid release in freely moving rats. Brain Research, Vol. 797 (1), p. 94-102. ISSN 0006-8993. Article.

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DOI: 10.1016/S0006-8993(98)00371-0

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 μ-opioid receptor-mediated mechanism mainly at extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative metabolism and affects glutamate and AA release by a μ-opioid receptor mediated mechanism acting also at nigral sites; and (iii) a μ-opioid receptor-mediated mechanism tonically controls at striatal sites extracellular AA and glutamate concentrations.

Item Type:Article
ID Code:4364
Status:Published
Refereed:Yes
Uncontrolled Keywords:Morphine, naloxone, dopamine metabolism, glutamate, ascorbic acid, striatum
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:Elsevier
ISSN:0006-8993
Deposited On:25 Aug 2010 11:48

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