Differential Effect of Central versus Parenteral Administration of Morphine Sulf ate on Regional Concentrations of Reduced Glutathione in Rat Brain

Abstract

Prior studies in rodents have shown significant depletion of reduced glutathione (GSH) in peripheral organs following acute systemic or central administration of opioids. However, little information exists on whether opioid administration affects concentrations of brain GSH. Recently, clinical observations have indicated acute declines of GSH concentrations in the cerebrospinal fluid of cancer patients after acute intracerebroventricular (ICV) morphine which may contribute to the development of organic behavioral brain syndromes associated with central opioid analgesia. Collectively these data led us to investigate the effect of acute systemic and central morphine on regional concentrations of GSH in rat brain. Systemic morphine had no effect on GSH concentrations in selected brain areas. In contrast, ICV morphine resulted in selective GSH depletion in the caudate nucleus, consistent with concurrent excitatory locomotive behavior. This change may have reflected morphine-induced oxidative stress together with increased metabolic activity within the extrapyramidal system.

Morphine or its withdrawal affects plasma malondialdehyde, vitamin E levels and absence or presence of abstinence signs in rats

“…Vitamin E levels were decreased in our M and M + N groups and, as shown in Figure 1, negatively correlated with the levels of free MDA (Pearson's correlation coefficient r = −0.466; P = 0.005), thus further indicating the altered oxidative and antioxidative status of the rats in the M and M + N groups. The reduced antioxidant power in the rats treated with morphine or morphine + naloxone is in line with the findings of other authors, showing a decrease in reduced glutathione levels after morphine exposure, 12 or in antioxidant enzymes in mice treated with heroin 4,6 …”

Oxidative stress induced by morphine in brain of rats fed with a protein deficient diet

“…Previous studies have shown significant depletion of GSH in peripheral organs following acute systemic or central administration of opioids. 9 The m-opioid receptor (MOR) the principal receptor involved in narcotic addiction, potentially play a key role in addiction, in combination with gene regulation and synaptic remodeling. 10 The MOR, which belongs to the family of seventransmembrane G-protein-coupled receptors, is a heavily N-glycosylated protein that regulates G proteins.…”

Assessment of Oxidative Damage Induced by Acute Doses of Morphine Sulfate in Postnatal and Adult Rat Brain

“…Previous studies have shown significant depletion of reduced glutathione (GSH) in peripheral organs following acute systemic or central administration of opioids [10]. One alternative to diminish the presence of endogenous free radicals induced by ageing and by the pathogenesis of many diseases requires the presence of glutathione (GSH) [11].…”

“…In this context, morphinedependent mice showed an increase in NO content in brain, which decreased by administration of melatonin, an important metabolite of serotonin (5-HT) [10]. 5-HT can capture free radicals present in damaged tissue [14], in addition to increasing oxidative metabolism by the presence of morphine [15].…”