Disulfiram attenuates morphine or methadone withdrawal syndrome in mice

Abstract

Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioid abstinence syndrome, which occurs as a result of opioid withdrawal. Opioid dependence in mice was induced by subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg for 10 consecutive days. To trigger a withdrawal syndrome, the opioid receptor antagonist, naloxone, was administered at a dose of 1 mg/kg (subcutaneous), and the severity of withdrawal signs was assessed individually. Interruption of chronic treatment with morphine or methadone by naloxone has led to the occurrence of opioid abstinence signs such as jumping, paw tremor, wet-dog shakes, diarrhea, teeth chattering, ptosis, and piloerection. Importantly, pretreatment with disulfiram (25, 50, and 100 mg/kg) reduced the intensity of withdrawal signs induced by naloxone in morphine or methadone-treated mice. These findings show the effectiveness of disulfiram in reducing opioid abstinence signs.

Xylopic acid from Xylopia aethiopica (Annonaceae) inhibits morphine tolerance in rats

“…Alterations of specific physiological functions are responsible for the individual signs of withdrawal observed 21 . The withdrawal signs investigated were diarrhea, weight loss, mean number of jumps per 60 minutes, and mean number of abdominal contractions 14,[22][23][24] . Research provides evidence suggesting an association of the cholinergic system with biological activity of opiates 25 .…”

“…Subsequent to administration of naloxone, animals were individually put into a transparent observation chamber and observed for occurrence of withdrawal signs (Figure 2). Both quantitative (increased frequency of jumps and abdominal contractions) and qualitative (diarrhea, weight loss) signs were noted according to work by de Corde A and colleagues 14 . Activity of XA (30 mg/kg) was blocked with selected antagonists yohimbine (2.5 mg/kg; p.o.…”

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

“…Moreover, DSF was reported to block cocaine-induced reinstatement in laboratory animals. Furthermore, DSF was found to be a useful drug candidate in opioid users [ 9 ], as well as in the treatment of non-substance-abuse disorders, such as pathological gambling [ 10 ]. However, the opposite effects were noted for DSF following cannabis smoke.…”