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

Dawid Gawliński,Kinga Gawlińska,Małgorzata Frankowska,Małgorzata Filip

doi:10.3390/nu12051462

Dawid Gawliński, Kinga Gawlińska + Show 2 more

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https://doi.org/10.3390/nu12051462

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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.

Highlights

In the global population, every fourth person suffers from mental illnesses throughout their life, the most common of which are depression, anxiety, substance use disorder, and schizophrenia [1,2,3]
In light of the above data and the small number of studies on the pathogenesis of developing addiction in females compared to studies in males, the purpose of this study was to determine the role of a maternal high-fat diet (HFD), high sugar-diet (HSD), and mixed diet (MD; rich in carbohydrate and fat) during pregnancy and lactation on the behavioral and neurochemical changes in female offspring in the aspect of cocaine addiction
We showed that a modified maternal diet during pregnancy and the lactation period is an important factor inducing impairments at the behavioral and neurochemical levels and a cocaine-seeking prone phenotype in female offspring

Summary

Introduction

Every fourth person suffers from mental illnesses throughout their life, the most common of which are depression, anxiety, substance (alcohol, drugs) use disorder, and schizophrenia [1,2,3]. Exposure to excessive or insufficient amounts of macronutrients (fats, sugars, proteins) can lead to morphological, molecular, and functional changes in the brains of offspring, predisposing them to the occurrence of behavioral disorders and mental diseases, such as increased impulsiveness, depression, Nutrients 2020, 12, 1462; doi:10.3390/nu12051462 www.mdpi.com/journal/nutrients. Nutrients 2020, 12, 1462 or anxiety, which further predispose them to the risk of developing substance use disorders later in life [5,6,7,8,9]. A maternal diet rich in fat provokes increased consumption and preference for palatable but unhealthy food in offspring [10,11,12], increased nicotine and ethanol self-administration [13,14], and disturbed behavioral reactions in animals regarding the administration of psychostimulant substances (reduced locomotor activity and amphetamine-induced behavioral sensitization) [15]

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