Effect of morphine on striatal dopamine metabolism and ascorbic acid and uric acid release in freely moving rats

Institute of Pharmacology, University of Sassari, Viale S. Pietro 43/B, 07100 Sassari, Italy
Brain Research (Impact Factor: 2.83). 02/1997; 745(1-2):173-182. DOI: 10.1016/S0006-8993(96)01146-8

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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    • "Preclinical investigations have identified multiple roles of purines in the brain, including energy metabolism, trophic functions, signaling, and neuromodulation (Boucsein C et al., 2003; Burnstock, 2008; Rathbone et al., 1999). Acute administration of morphine enhances purine catabolism lowering cell energy, a condition that reverts following drug discontinuation, but not with chronic administration in rodents (Di Francesco et al., 1998; Enrico et al., 1997; Liu et al., 2003, 2007). In type I diabetes, a model of chronic metabolic disease, increased mithochondrial purine catabolism is reactive to antioxidant offenses and has been measured by changes in hypoxanthine, guanine, guanosine, and xanthosine, similar to what found in plasma of OD patients (Kristal et al., 1999). "
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    Human Psychopharmacology Clinical and Experimental 12/2009; 24(8):666-75. DOI:10.1002/hup.1068 · 1.85 Impact Factor
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    • "First, the opiate was able to induce the production of ROS. 1. It has been demonstrated that heroin or morphine are able to induce the production of ROS in several cells, such as, PC12 cells (Oliveira et al. 2002), and glomerular mesangial cells (Singhal, et al. 1994); 2. It has been demonstrated that morphine is able to induce an increase in DA and xanthine oxidative metabolism (Desole et al. 1996; Enrico et al. 1997). It is well known that ROS can be generated during both DA (Spina and Akil 1991) and xanthine oxidase (XO) metabolism (Becker et al. 1993), xanthine can be oxidized by XO and produce superoxide anion (O 2 .À ), and dopamine can be oxidized by O 2 .À through monoamine oxidase-B (MAO-B) in humans, giving rise to dihydroxyphenylacetic acid (DOPAC) and H 2 O 2 (Olanow and Tatton 1999). "
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