Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

Abstract

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

Western Diet Consumption During Development: Setting the Stage for Neurocognitive Dysfunction

“…Perinatal exposure to a WD can dysregulate reward-motivated behavior, even when offspring are reared on a standard chow diet ( Naef et al, 2008 , 2011 ; Ong and Muhlhausler, 2011 ; Morganstern et al, 2013 ; Wu et al, 2013 ; Grissom et al, 2015 ; Peleg-Raibstein et al, 2016 ; Roversi et al, 2016 ; Paradis et al, 2017 ; Sarker et al, 2019 ; Gawliński et al, 2020 ). For example, when dams were exposed to a WD (60% kcals from fat) pre-conception there were no differences in sensitivity to amphetamine, as indicated by amphetamine-induced locomotor activity, or preference for alcohol in offspring.…”

“…For example, when dams are fed a WD from gestational day 1 until end of lactation, male pups show a transient enhanced fat preference at PN25 that normalizes by PN95 ( Paradis et al, 2017 ). Female offspring of dams fed a high sugar diet (44% kcals from sucrose) were more responsive to cue and cocaine-induced reinstatement of lever pressing ( Gawliński et al, 2020 ). Finally, maternal consumption of a high fat/high sucrose diet from gestation day 5 until end of lactation increased operant responding for nicotine infusion in the male offspring ( Morganstern et al, 2013 ).…”

“…Similar to the effects described in the earlier sections on anxiety, learning, and memory, an obesogenic phenotype is not required for there to be differences in reward-motivated behavior associated with perinatal WD consumption. While some studies observed that a perinatal WD increases body weight and adiposity and promotes disturbances in metabolism (e.g., insulin insensitivity) in offspring at weaning ( Naef et al, 2008 ; Ong and Muhlhausler, 2011 ; Morganstern et al, 2013 ; Peleg-Raibstein et al, 2016 ; Paradis et al, 2017 ; Song et al, 2020 ) and as adults ( Naef et al, 2011 ; Ong and Muhlhausler, 2011 ; Morganstern et al, 2013 ; Peleg-Raibstein et al, 2016 ; Paradis et al, 2017 ; Sarker et al, 2019 ; Song et al, 2020 ), other studies found no such differences ( Wu et al, 2013 ; Ong and Muhlhausler, 2014 ; Grissom et al, 2015 ; Roversi et al, 2016 ; Gawliński et al, 2020 ), even when the dams were heavier as a result of the obesogenic diet ( Wu et al, 2013 ; Ong and Muhlhausler, 2014 ). Again, these differences could be reflective of the type of WD being used, with those higher in fat leading to more severe metabolic consequences, and/or also the different rodent strains being used.…”

“…Despite offspring showing enhanced preference for junk food at both time points, ACB gene expression for mu opioid receptor is increased and dopamine transporter is decreased during adolescence, while changes occur in the opposite direction at adulthood ( Ong and Muhlhausler, 2011 ). In addition to facilitating cocaine-induced reinstatement, maternal exposure to a high sucrose diet is associated with higher striatal levels of melanocortin 4 receptor in the adult offspring ( Gawliński et al, 2020 ). Grissom and colleagues found that attention and impulsivity deficits observed after perinatal WD exposure during gestation and lactation were linked with overexpression of DNMT1 in the mPFC, which is involved in DNA methylation, catechol-o-methyltransferase, which is an enzyme that degrades catecholamines like dopamine, δ-opioid receptor, whose activation can lead to increased extracellular dopamine ( Burns et al, 2019 ), and cannabinoid receptor 1, which regulates the expression of D2R ( Blume et al, 2013 ; Grissom et al, 2015 ).…”

Maternal dietary patterns are associated with susceptibility to a depressive-like phenotype in rat offspring

“…Epidemiological and experimental data from recent years indicate that, through pregnancy and lactation, maternal modified diets (e.g., high-caloric, rich in fat, sugar, or protein) increase offspring’s predisposition to the development of diseases such as obesity, metabolic syndrome, and diabetes. Moreover, the lack of a properly balanced diet and obesity during pregnancy and lactation can lead to morphological, molecular, and functional changes in the offspring’s brain, predisposing the offspring to the occurrence of behavioral disorders and mental diseases ( de la Garza et al, 2019 ; Faa et al, 2014 ; Gawlińska et al, 2020 ; Gawliński et al, 2020a , 2020b ; Sullivan et al, 2015 ). For example, maternal overnutrition and consumption of a diet rich in fat are associated with an increased risk of mental and neurodevelopmental disorders including depression ( Gawlińska et al, 2019 ), attention-deficit hyperactivity disorder (ADHD) ( Buss et al, 2012 ; Chen et al, 2014 ; Rodriguez et al, 2008 ), autism spectrum disorder (ASD) ( Getz et al, 2016 ; Krakowiak et al, 2012 ; Reynolds et al, 2014 ) and schizophrenia in adulthood ( Jones et al, 1998 ; Schaefer et al, 2000 ).…”