The dopamine beta-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats

Craving for chocolate is a common phenomenon which may evolve to an addictive-like behavior and contribute to obesity. Nepicastat is a selective dopamine ?-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified if nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent reinstatement of chocolate seeking in rats. Nepicastat (25, 50, and 100 mg/kg, i.p.) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under Fixed Ratio (FR) 10 (FR10) and Progressive Ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. Nepicastat effect on reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 days. Nepicastat dose-dependently suppressed reinstatement of lever-responding triggered by a "priming" of the chocolate solution together with cues previously associated to the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of chocolate solution and regular food pellets and suppressed reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover they suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.