ArticleProceedings of the National Academy of Sciences of the United States of America2021
Early life adversity promotes resilience to opioid addiction-related phenotypes in male rats and sex-specific transcriptional changes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 67 citations in OpenAlex.
- Early life adversity disrupts adult social reward motivation.bioRxiv : the preprint server for biology · 2026Article
- Examining the impact of adolescent social isolation on oxycodone sensitization.Psychopharmacology · 2026Article
- Combined maternal separation and limited bedding-nesting increase goal tracking, delay discounting, and impulsive action, and moderate sign-tracking-perseverance associations in male rats.BMC neuroscience · 2026Article
- Gestational choline supplementation regulates hippocampal granule neuron development and emotion-like behavior.Communications biology · 2026Article
- Investigating milk-derived extracellular vesicles as mediators of maternal stress and environmental intervention.Molecular psychiatry · 2026Article
- Maternal separation disrupts noradrenergic control of adult coping behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Investigating milk-derived extracellular vesicles as mediators of maternal stress and environmental intervention.bioRxiv : the preprint server for biology · 2025Article
- Single-Nucleus Transcriptomics of the Nucleus Accumbens Reveals Cell-Type-Specific Dysregulation in Adolescent Macaques with Depressive-Like Behaviors.Neuroscience bulletin · 2025Article
- Retrotransposons and the brain: Exploring a complex relationship between mobile elements, stress, and neurological health.Neurobiology of stress · 2025Review
- Unraveling sex differences in maternal and paternal care impacts on social behaviors and neurobiological responses to early-life adversity.Frontiers in neuroendocrinology · 2025Review
- Opioid drug seeking after early-life adversity: a role for delta opioid receptors.Addiction neuroscience · 2024Article
- Enhancing translation: A need to leverage complex preclinical models of addictive drugs to accelerate substance use treatment options.Pharmacology, biochemistry, and behavior · 2024Review
- Sex-dependent effects of acute stress in adolescence or adulthood on appetitive motivation.Psychopharmacology · 2024Article
- A Double Hit of Social and Economic Stress in Mice Precipitates Changes in Decision-Making Strategies.Biological psychiatry · 2024Article
- Sex differences in offspring risk and resilience following 11β-hydroxylase antagonism in a rodent model of maternal immune activation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Neuroscience in addiction research.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats.Neurobiology of stress · 2024Article
- Translational models of stress and resilience: An applied neuroscience methodology review.Neuroscience applied · 2024Review
- Transcriptional signatures of early-life stress and antidepressant treatment efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Experiencing some early life adversity can have an "inoculating" effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown, and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal days 2 to 9 and their dams were exposed to a low-resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but in males, LBN reduced impulsive choice compared to controls. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. These effects of LBN on addiction-related behaviors were not found in females. Because the nucleus accumbens (NAc) mediates these behaviors, we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced the frequency of spontaneous excitatory postsynaptic currents in males, but a similar effect was not observed in females. Only in males did LBN prevent a morphine-induced increase in the AMPA/NMDA ratio. RNA sequencing was performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients.
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