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: 2.84).
02/1997; 745(1-2):173-182. DOI: 10.1016/S0006-8993(96)01146-8
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.
Available from: Paolo Mannelli
- "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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ABSTRACT: More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant compounds and purine metabolism. We examined perturbations of neurotransmitter-related pathways in opioid dependence (OD).
In this preliminary study, we used a targeted metabolomics platform to explore whether biochemical changes were associated with OD by comparing OD individuals (n = 14) and non-drug users (n = 10).
OD patients undergoing short-term methadone detoxification showed altered oxidation-reduction activity, as confirmed by higher plasma levels of alpha- and gamma-tocopherol and increased GSH/GSSG ratio. OD individuals had also altered purine metabolism, showing increased concentration of guanine and xanthosine, with decreased guanosine, hypoxanthine and hypoxanthine/xanthine and xanthine/xanthosine ratios. Other drug use in addition to opioids was associated with partly different biochemical changes.
This is a preliminary investigation using metabolomics and showing multiple peripheral alterations of metabolic pathways in OD. Further studies should explore the metabolic profile of conditions of opioid abuse, withdrawal and long-term abstinence in relation to agonist and antagonist treatment and investigate biochemical signatures of opioid substances and medications.
Available from: Qiusheng Zheng
- "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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ABSTRACT: Extensive but fragmentary studies have shown: (i) heroin, morphine and opiates are able to induce reactive oxygen species (ROS) formation in several cells, (ii) they decrease the antioxidant defense system including enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and antioxidants, glutathione (GSH), Se, and vitamins. This study is to investigate the oxidative damage to DNA, proteins, and lipids in brain of mice administered heroin via intraperitoneal injection, and the effects of verbascoside and luteolin on this damage. All the indices of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl group and malondialdehyde (MDA) contents increased significantly compared to those of controls in the brains of heroin-administered mice, while the indices related to the in vivo antioxidative capacity, such as the ratio of GSH and oxidized glutathione (GSSG), and activities of SOD, CAT and GPx in the brain, and total antioxidant capacity (TAC) in serum significantly decreased. When heroin-dependent mice were treated with verbascoside or luteolin, oxidative stress status was limited.
- ". UA has been shown to prevent the autoxidation of dopamine (Church and Ward 1994) and maintain ascorbic acid in a reduced state (Enrico et al. 1997) and has recently been implicated as a therapeutic agent protecting against peroxynitrate-initiated neuronal diseases (Hooper et al. 1998). In the present study, catecholamine and ascorbic acid levels were consistently higher in the brain regions with increased UA levels (see Table 1), further supporting the role of UA as a component of the neuronal antioxidant pool. "
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ABSTRACT: The effect of purine enzyme inhibition on catecholamine metabolism was investigated in guinea pigs. Catecholamine levels were measured in the nigrostriatal brain structures of male guinea pigs following treatment with allopurinol (a xanthine oxidase inhibitor; 250 mg/kg i.p.) or allantoxanimide (a uricase inhibitor; 200 mg/kg i.p.) once a day for 4 days. Tissue was analyzed from the striatum and the substantia nigra. Norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid, and uric acid were quantified with electrochemical and ultraviolet detection following separation by liquid chromatography. Allopurinol had no effect on nigrostriatal dopamine levels but decreased DOPAC levels (P<0.05) in the striatum. Allantoxanimide increased norepinephrine levels and decreased DOPAC levels in the striatum (P<0.05). Allopurinol decreased uric acid levels in the striatum and substantia nigra (P<0.05). Allantoxanimide increased uric acid levels in the striatum and the substantia nigra (P<0.05). These results indicate that alterations in purinergic enzyme activity can influence catecholamine metabolism within the nigrostriatal system of the guinea pig.
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