Limited Modulation of the Abuse-related Behavioral Effects of D-methamphetamine by Disulfiram

Disulfiram (Antabuse), an acetaldehyde dehydrogenase and dopamine-beta hydroxylase inhibitor, has shown promise in preclinical and clinical studies as a pharmacotherapy for cocaine addiction. However, the extent to which disulfiram may alter the abuse-related behavioral effects of related psychostimulants, such as methamphetamine, is unknown. Here, the therapeutic potential of disulfiram was evaluated by examining its impact on the reinforcing and discriminative stimulus effects of d-methamphetamine in adult rhesus monkeys (N = 4 per group). In subjects trained to respond for injections of methamphetamine or food delivery, i.v. methamphetamine (.001-.032 mg/kg) maintained dose-related and stable levels of self-administration in all subjects. Pretreatment with disulfiram (5.6 mg/kg) produced a significant downward shift in the d-methamphetamine dose-response function; surprisingly, lower and higher pretreatment doses (3.0 mg/kg; 10 mg/kg) were ineffective. Also, disulfiram (3-10 mg/kg) did not significantly alter food-maintained responding or, in subjects trained to discriminate the effects of cocaine from vehicle, the ability of d-methamphetamine (.032-.32 mg/kg) to substitute for cocaine. Taken together, the present data reveal dose-dependent effects of disulfiram in modifying some of the abuse-related effects of d-methamphetamine and provides support for future investigations examining the capacity of disulfiram as a treatment for d-methamphetamine abuse. (PsycINFO Database Record (c) 2018 APA, all rights reserved).