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Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition.

ABSTRACT: Epidemiological studies have shown an association between maternal overnutrition and increased risk of the progeny for the development of obesity as well as psychiatric disorders. Animal studies have shown results regarding maternal high-fat diet (HFD) and a greater risk of the offspring to develop obesity. However, it still remains unknown whether maternal HFD can program the central reward system in such a way that it will imprint long-term changes that will predispose the offspring to addictive-like behaviors that may lead to obesity. We exposed female dams to either laboratory chow or HFD for a period of 9 weeks: 3 weeks before conception, during gestation and lactation. Offspring born to either control or HFD-exposed dams were examined in behavioral, neurochemical, neuroanatomical, metabolic and positron emission tomography (PET) scan tests. Our results demonstrate that HFD offspring compared with controls consume more alcohol, exhibit increased sensitivity to amphetamine and show greater conditioned place preference to cocaine. In addition, maternal HFD leads to increased preference to sucrose as well as to HFD while leaving the general feeding behavior intact. The hedonic behavioral alterations are accompanied by reduction of striatal dopamine and by increased dopamine 2 receptors in the same brain region as evaluated by post-mortem neurochemical, immunohistochemical as well as PET analyses. Taken together, our data suggest that maternal overnutrition predisposes the offspring to develop hedonic-like behaviors to both drugs of abuse as well as palatable foods and that these types of behaviors may share common neuronal underlying mechanisms that can lead to obesity.

SUBMITTER: Peleg-Raibstein D

PROVIDER: S-EPMC5315546 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition.

Peleg-Raibstein D D Sarker G G Litwan K K Krämer S D SD Ametamey S M SM Schibli R R Wolfrum C C

Translational psychiatry 20161004 10

Epidemiological studies have shown an association between maternal overnutrition and increased risk of the progeny for the development of obesity as well as psychiatric disorders. Animal studies have shown results regarding maternal high-fat diet (HFD) and a greater risk of the offspring to develop obesity. However, it still remains unknown whether maternal HFD can program the central reward system in such a way that it will imprint long-term changes that will predispose the offspring to addicti ...[more]

PMID: 27701408

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Project description:Background and objectivesStudies in low-and middle-income countries where nutrition transition is underway provides mixed evidence of double burden of maternal overnutrition and child undernutrition among mother-child pairs. Shifting dietary pattern and rapid increase in overweight/obesity among adults with persistent child undernutrition indicate that India is experiencing nutrition transition and double burden of malnutrition. Hence, the study explores the presence of and the factors associated with mother-child dyads of over- and undernutrition in India.Methods and materialsThe study uses National Family Health Survey 2015-16 data. The analytic sample consists of 28,817 weighted mother-child pairs where an overweight/obese mother is paired with an undernourished child. The nutritional status of children is defined according to WHO 2006 child growth standards as underweight (i.e., low weight-for-age), stunting (i.e., low height-for-age) and wasting (i.e., low weight-for-height). Maternal overweight/obesity (i.e., BMI ≥ 25 kg/m2) is defined using adult BMI criterion. Descriptive, bivariate, and adjusted multivariable logistic regression analysis are conducted.ResultsOf the overweight/obese mothers, 21.3%, 26.5%, and 14% have underweight, stunted, and wasted children respectively. In adjusted models, maternal short stature (aOR: 2.94, 95% CI: 2.30-3.75), age of child (aOR: 3.29, 95% CI: 2.76-3.92), and poorest wealth status (aOR: 2.01, 95% CI: 1.59-2.54) are significant predictors of overweight/obese mothers and stunted child pairs. Similarly, poor wealth status (aOR: 1.68, 95% CI:1.32-2.14), maternal stature (aOR: 2.70, 95% CI: 2.08-3.52), and child aged 2-5 years (aOR: 1.77, 95% CI:1.51-2.08) are also significantly associated with higher occurrence of overweight/obese mother and-underweight child pairs.ConclusionFindings of the study are consistent with the phase of nutrition transition and double burden of malnutrition. The paper concludes with suggestions to improve the socioeconomic condition, more strategic nutrition specific investments and policy interventions to eliminate all forms of malnutrition for achieving SDGs.

Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Six the most addictive and harming drugs of abuse (morphine 20 mg/kg, heroin 10 mg/kg, ethanol 2 g/kg, nicotine 1 mg/kg, methamphetamine 2 mg/kg or cocaine 25 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as rewarding in mice and further tested in our laboratory. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naïve animals were prepared for each time point. Design of the experiment assumed pooling of two animals per each array and using of three independent arrays per group. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.

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Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition.

Publications

Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition.

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