title: The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats.
abstract: Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with 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 the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results 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.
authors.affiliation: Neuroscience Institute, National Research Council of Italy, Section of Cagliari, S.S. 554 km. 4,500, I-09042 Monserrato (CA), Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zaru
authors.forename: Paola
authors.initials: P
authors.lastname: Maccioni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000818:Animals; D002099:Cacao / Q000737:chemistry*; D002182:Candy; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D005502:Food; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D013871:Thiones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007093:Imidazoles; D013871:Thiones; D004299:Dopamine beta-Hydroxylase; C109487:nepicastat