The Positive and Negative Outcome of Morphine and Disulfiram Subacute Co-Administration in Rats in the Absence of Ethanol Challenge

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.

Treatment with dopamine β-hydroxylase (DBH) inhibitors prevents morphine use and relapse-like behavior in rats

“…Disulfiram (DSF; N,N,N',Ntetraethylthiuram disulfide, Polfa Warszawa, Warszawa, Poland) suspended in 0.1% methylcellulose (Sigma Aldrich, St. Louis, MO, USA) and nepicastat (NEP, BOC Sciences New Yorke, NY, USA) suspended in saline with 1.5% (v/v) DMSO (Sigma Aldrich, St. Louis, MO, USA) and 1.5% ethanol (POCH, Gliwice, Poland) were pre-administered 120 min, ip (1 ml/kg). Doses and pre-administration time of both DBH inhibitors were chosen based on previous research [13,14,24].…”

“…Following extinction training, morphine (5 mg/kg, ip) or the morphine-associated cue-induced reinstatement was tested in the same animals. The dose of DSF or NEP was selected based on the acute drug effect and previous research [13,14,24] (Fig. 1).…”