Effect of morphine on striatal dopamine metabolism and ascorbic acid and uric acid release in freely moving rats
ABSTRACT Recent ex vivo findings have shown that morphine increases dopamine (DA) and xanthine oxidative metabolism and ascorbic acid (AA) oxidation in the rat striatum. In the present study, we evaluated the effects of subcutaneous daily morphine (20 mg/kg) administration on DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), AA and uric acid in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection. On the first day, morphine administration caused a significant increase in extracellular DA, DOPAC, HVA, AA and uric acid concentrations over a 3 h period after morphine. In all treated rats (n=7), individual concentrations of DOPAC+HVA were directly correlated with individual AA and uric acid concentrations. Last morphine administration on the 4th day increased DOPAC, HVA, AA and uric acid concentrations but failed to increase those of DA. Individual DOPAC+HVA concentrations were still directly correlated with individual AA and uric acid concentrations. These results suggest that systemic morphine increases both striatal DA release and DA and xanthine oxidative metabolism. Only the former effect undergoes tolerance. The increase in DA oxidative metabolism is highly correlated with that of xanthine. The subsequent enhancement in reactive oxygen species production may account for the increase in extracellular AA.
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ABSTRACT: The effects of dl -fenfluramine, dl -5-hydroxytryptophan(5-HTP) and fluoxetine on ethanol-induced striatal ascorbic acid (AA) release in rat were studied by microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg, i.p.) stimulated striatal AA release to more than 200% above the baseline. dl -Fenfluramine (20 mg/kg, i.p. or 40 mug/rat, i.c.v.), 10 min before ethanol administration, markedly inhibited ethanol-induced AA release. A similar result was also observed following dl -5-HTP (100 mg/kg, i.p.) administration. However, fluoxetine (10, 30 mg/kg, i.p.) showed no antagonistic effect on ethanol-induced AA release. The suppressing effect of dl -fenfluramine and dl -5-HTP on ethanolinduced AA release could be reversed by the 5-HT receptor antagonist cyproheptadine (10 mg/kg, s.c.). All these drugs had no effect on basal AA release. The results give a first evidence for the involvement of central serotonergic system, and suggest that differential activities may exist between dl -fenfluramine, dl -5-HTP and fluoxetine in regulating ethanol-induced AA release in rat striatum.Addiction Biology 01/1998; 3(3):295-308. · 5.91 Impact Factor
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ABSTRACT: Nutritional status including vitamin A could explain some of the developmental deformities observed in cultivated teleosts, including Atlantic cod (Gadus morhua). In the present study we aimed to investigate the transcriptional effect of retinoic acid (RA) on bone related genes using Atlantic cod craniofacial explants tissue cultures. Two different osteoblast specific osteocalcin/bone gla protein isoforms were discovered in cod. Transcription of both isoforms was up-regulated following RA treatment of 65 dph cod lower jaw explants. In contrast, transcripts coding for genes related to bone resorption and osteoclast activity, matrix metalloproteinase 9 and cathepsin K were down-regulated following RA treatment. This could be linked to the decreased transcriptional ratio between receptor activator of nuclear factor kappa-B ligand rankl and osteoprotegerin observed in the same tissue samples. RA treatment of juvenile explants had no effect on runt-related transcription factor 2 and osterix mRNA levels. However, osterix was significantly down-regulated in 25 dph cod head explants following RA treatment. In situ hybridizations revealed differential spatial distribution of the two isoforms and the predominant expression of cathepsin K in bone surrounding tissues. The present study indicates that RA causes a shift in the balance between osteoclast activity and osteoblast activity in favor of the latter.Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 10/2011; 161(2):174-84. · 2.20 Impact Factor
- Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan - YAKUGAKU ZASSHI-J PHARM SOC J. 01/2006; 126(8):671-675.