Disulfiram inhibits chocolate self-administration and reinstatement to chocolate seeking in rats

• New insights on the pharmacological profile of the “old” drug, disulfiram
• Disulfiram suppressed self-administration of chocolate and chocolate seeking in rats.
• The peculiar time-course of these effects suggests a novel mechanism of action.

We recently found that the dopamine β-hydroxylase (DBH) inhibitor, nepicastat, reduced chocolate self-administration and reinstatement of chocolate-seeking behavior in free-fed rats and self-administration of regular food pellets in food-restricted rats. Here we show that disulfiram reproduced all these effects but exhibited a considerably different time-course. Wistar rats were trained to lever-respond for a chocolate solution (free-fed rats) or regular food pellets (food-restricted rats) under the Fixed Ratio (FR) 10 (FR10) schedule of reinforcement. Once lever-responding stabilized, rats were exposed to sessions under FR10 and Progressive Ratio (PR) schedule and reinstatement sessions. Acutely administered disulfiram (0, 25, 50, and 100 mg/kg, i.p.) inhibited, with similar potency and effectiveness, lever-responding for chocolate solution and regular food pellets under the FR10 schedule. Disulfiram-induced inhibition of lever-responding for chocolate solution and regular food pellets showed a biphasic time-course: an early inhibition at 2 h, which subsided within 24 h, and a second long-lasting inhibition from 48 to 96 h. Administered 48 h beforehand, disulfiram reduced lever-responding for chocolate solution under the PR schedule and prevented cue-induced reinstatement of chocolate-seeking behavior. Spontaneous locomotor activity was reduced at 2 but not 48 h after disulfiram administration. These results indicate that disulfiram reduced food seeking and consumption elicited by high palatability or appetite. It is suggested that the delayed inhibitory effect of disulfiram is likely mediated by a novel mechanism distinct from blockade of DBH or aldehyde dehydrogenase.