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BACKGROUND: Despite considerable knowledge that prenatal ethanol exposure can lead to devastating effects on the developing fetus, alcohol consumption by pregnant women remains strikingly prevalent. Both clinical and basic research has suggested that, in addition to possible physical, behavioral, and cognitive deficits, gestational exposure to alcohol may lead to an increased risk for the development of later alcohol-related use and abuse disorders. The current work sought to characterize alterations in endogenous opioid signaling peptides and gene expression produced by ethanol exposure during the last days of gestation., METHODS: Experimental subjects were 4-, 8-, and 12-day old infant rats obtained from pregnant females that were given daily intubations of 0, 1, or 2g/kg ethanol during the last few days of gestation (GDs 17-20). Using real-time RT-PCR, western blotting analysis, and enzyme immunoassays, we examined mRNA and protein for three opioid receptors and ligands in the nucleus accumbens, ventral tegmental area, and hypothalamus., RESULTS: Three main trends emerged - (1) mRNA for the majority of factors was found to upregulate across each of the three postnatal ages assessed, indicative of escalating ontogenetic expression of opioid-related genes; (2) prenatal ethanol significantly reduced many opioid peptides, suggesting a possible mechanism by which prenatal exposure can affect future responsiveness towards ethanol; and (3) the nucleus accumbens emerged as a key site for ethanol-dependent effects, suggesting a potential target for additional assessment and intervention towards understanding the ethanol's ability to program the developing brain., CONCLUSION: We provide a global assessment of relatively long-term changes in both opioid gene expression and protein following exposure to only moderate amounts of ethanol during a relatively short window in the prenatal period. These results suggest that, while continuing to undergo ontogenetic changes, the infant brain is sensitive to prenatal ethanol exposure and that such exposure may lead to relatively long-lasting changes in the endogenous opioid system within the reward circuitry. These data indicate a potential mechanism and target for additional assessments of ethanol's ability to program the brain, affecting later responsiveness towards the drug. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmental enrichment (EE) is one experimental manipulation that induces changes in the brain. However, it is important to distinguish between physical and social components of enrichment. To this end we established four groups of rats reared in different enriched environments during the adolescent period. Our results indicate heightened social memory and increased spine density in dentate gyrus specifically in socially enriched animals. Physical enrichment increased spine density in CA1. Dopamine D2 receptor expression in hippocampus was decreased across all enrichment conditions. Altogether, our results demonstrate differing effects of physical and social enrichment, supporting an important role for environment in synaptogenesis, behavior, and dopaminergic signaling. © 2020 The Authors

Research suggests that addictive traits are indeed heritable, but very few preclinical studies have explored transgenerational effects of paternal alcohol exposure. The present study addressed this gap in knowledge. We explored whether offspring of ethanol-exposed sires would be more likely to accept ethanol than descendants of water-exposed and control sires. We also investigated whether the second generation of ethanol-exposed descendants would accept ethanol more than controls and were more or less likely to experience anxiety-like behavior in behavioral assessments. We exposed male rats to repeated binge doses of alcohol (4 g/kg/day across 8 days), water, or left them untreated and mated them with untreated females. We then bred the offspring of these rats to test transgenerational effects of paternal alcohol exposure. We tested 14-day-old offspring from the first and second filial generation for their acceptance of ethanol and water, and measured anxiety-like behavior in 38-day-old, second-generation offspring using an elevated plus maze. The results indicate that offspring of ethanol-exposed sires increase ethanol acceptance in the first generation compared to untreated controls, whereas in the second-generation increased ethanol acceptance vs. these controls is seen in descendants of both ethanol- and vehicle-treated sires. At adolescence, the second generation of rats derived from alcohol-exposed sires exhibited significantly more time spent in the open arms and significantly more arm entries than any other group. The present study suggests that parental ethanol exposure is associated with lingering effects in the infant and adolescent offspring. The second filial generation was also found to be affected, albeit similarly by grandparental ethanol exposure or by the stress of the vehicle administration. Copyright © 2021 Elsevier Inc. All rights reserved.

Early life neglect increases risk for the development of psychopathologies during childhood and adulthood, including depression and anxiety disorders. We recently reported epigenetic changes in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3 (ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting Protein (TPPP). To validate the role of these genes in depression risk, secondary analyses were conducted of gene expression data obtained from medial prefrontal cortex (mPFC) tissue of mice subjected to a model of maternal neglect which included maternal separation and early weaning (MSEW). Anxiety and depression-like phenotype data derived using the elevated plus maze (EPM) and forced swimming test (FST), respectively, were also available for secondary analyses. Behavioral tests were conducted in MSEW and control adult male mice when they were between 65 and 80days old. ID3, GRIN1 and TPPP gene expression in the mPFC were found to significantly predict behavioral differences in the EPM and FST. These results further support the role of these genes in the etiology of depressive and anxiety phenotypes following early life stress. Copyright © 2016. Published by Elsevier B.V.

Background: Approximately 10 to 15% of women consume alcohol (ethanol [EtOH]) during pregnancy in the United States. Even low amounts of EtOH consumption during pregnancy can elicit long-term consequences. Prenatal experience with as few as 3 drinks has been associated with increase problem drinking in adulthood. Such effects are corroborated in rodents; however, the underlying neural adaptations contributing to this effect are not clear. In the current set of experiments, we investigated whether changes in EtOH responding following prenatal EtOH exposure involved kappa opioid receptor activation and expression. Methods: Sprague-Dawley rats were prenatally exposed to low levels of alcohol (1.0 g/kg) during late gestation (gestational days 17 to 20 [GD17-20]) via intragastric intubation of pregnant dams. Following birth, EtOH intake, kappa- and mu-opioid-induced place conditioning, and kappa opioid receptor expression in mesolimbic brain regions were assessed in infant rats (postnatal days 14 to 15 [PD14-15]) that were offspring of dams given EtOH, vehicle, or untreated, during pregnancy. Results: Animals exposed to prenatal alcohol drank more alcohol later in life and exhibited significant changes in the kappa opioid system. While control subjects found kappa opioid activation aversive, animals exposed to EtOH prenatally exhibited either no aversion or appetitive responding. Further analysis revealed that synaptosomal kappa opioid receptor expression was significantly decreased in brain areas implicated in responding to EtOH. Conclusions: Overall, these data suggest that prenatal EtOH affects kappa opioid function and expression and that these changes may be involved in increased drinking later in life. © 2014 by the Research Society on Alcoholism.

Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus-pituitary-adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest.