Abstract
Recently, a well-known anti-alcohol agent, disulfiram (DSF), has gain much interest, as it was found to be effective in the treatment of cocaine abusers, thus also giving hope for patients addicted to opioids and other illicit drugs. Therefore, this study was aimed to investigate the possible outcome that might occur within the subacute co-administration of both morphine (MRF) and DSF in rats, but in the absence of ethanol challenge. As observed, intraperitoneal DSF dose-dependently enhanced MRF-mediated analgesia with the maximal efficacy at a dose of 100 mg/kg. Furthermore, MRF-induced tolerance and aggressive behavior were significantly reduced by DSF (100 mg/kg, i.p.) in comparison to MRF solely. Nonetheless, significant blood biochemical markers of hepatotoxicity were found (i.e., alteration in the levels of glutathione, blood urea nitrogen, etc.), following a combination of both drugs. Likewise, histological analysis of liver tissue revealed severe changes in the group of DSF + MRF, which includes swelling, cell death, damage to certain vessels, and hemorrhages into the liver parenchyma. Our findings indicate that DSF should be used with extreme caution, especially within the course of subacute concomitant use with MRF, as several possible side effects may take place.
Highlights
MRF was dissolved in 0.9% NaCl, whereas DSF was suspended in 0.1% solution of methylcellulose
Compared with the effect induced by the vehicle, the lowest dose of DSF (25 mg/kg, i.p.) resulted in hyperalgesia, starting from the MPE value equal
By increasing the dose of DSF to 50 or 100 mg/kg, the strongest effect and the maximal activity was reached within 10-14 days of the experiment
Summary
Intraperitoneal DSF dosedependently enhanced MRF-mediated analgesia with the maximal efficacy at a dose of 100 mg/kg. Our findings indicate that DSF should be used with extreme caution, especially within the course of subacute concomitant use with MRF, as several possible side effects may take place. Currently, there is no effective drug to treat opioid abuse, detoxification can be nicely facilitated by using dose-tapered opioid agonists (mainly methadone) [1]. It seems that detoxification, and reduction in the use of the drug, in contrast to the rehabilitation of such patients, is quite complicated
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