Abstract

Maternal diet significantly influences the proper development of offspring in utero. Modifications of diet composition may lead to metabolic and mental disorders that may predispose offspring to a substance use disorder. We assessed the impact of a maternal high‐sugar diet (HSD, rich in sucrose) consumed during pregnancy and lactation on the offspring phenotype in the context of the rewarding and motivational effects of cocaine and changes within the central melanocortin (MC) system. Using an intravenous cocaine self‐administration model, we showed that maternal HSD leads to increased relapse of cocaine‐seeking behavior in male offspring. In addition, we demonstrated that cocaine induces changes in the level of MC‐4 receptors in the offspring brain, and these changes depend on maternal diet. These studies also reveal that an MC‐4 receptor antagonist reduces the reinstatement of cocaine‐seeking behavior, and offspring exposed to maternal HSD are more sensitive to its effects than offspring exposed to the maternal control diet. Taken together, the results suggest that a maternal HSD and MC‐4 receptors play an important role in cocaine relapse.