ArticlePloS one2014
Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
- Environmental enrichment as an intervention to prevent behavioral and neurobiological consequences of maternal separation in rodents: a scope review.Neurobiology of stress · 2026Article
- Biomarkers for complex post-traumatic stress disorder: translational and evolutionary perspectives.Frontiers in psychiatry · 2026Article
- Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets.Current neuropharmacology · 2024Review
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex.Neurobiology of learning and memory · 2021Article
- Influence of Childhood Maltreatment, Adulthood Stressful Life Events, and Affective Temperaments on Premenstrual Mental Symptoms of Nonclinical Adult Volunteers.Neuropsychiatric disease and treatment · 2020Article
- The microbiota-gut-brain axis: An emerging role for the epigenome.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Unraveling the epigenetic landscape of depression: focus on early life stress .Dialogues in clinical neuroscience · 2019Review
- Dissecting the Roles of GABA and Neuropeptides from Rat Central Amygdala CRF Neurons in Anxiety and Fear Learning.Cell reports · 2019Article
- The impact of maternal separation and isolation stress during stress hyporesponsive period on fear retention and extinction recall memory from 5-week- to 1-year-old rats.Experimental brain research · 2019Article
- Maternal Deprivation Enhances Contextual Fear Memory via Epigenetically Programming Second-Hit Stress-Induced Reelin Expression in Adult Rats.The international journal of neuropsychopharmacology · 2018Article
- Neurotensin and neurotensin receptor 1 mRNA expression in song-control regions changes during development in male zebra finches.Developmental neurobiology · 2018Article
- Early adolescent adversity inflates threat estimation in females and promotes alcohol use initiation in both sexes.Behavioral neuroscience · 2018Article
- miR‑377 targets CUL4A and regulates metastatic capability in ovarian cancer.International journal of molecular medicine · 2018Article
- Epigenetic Landscapes of the Adversity-Exposed Brain.Progress in molecular biology and translational science · 2018Review
- A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Neuroepigenetics of Post-Traumatic Stress Disorder.Progress in molecular biology and translational science · 2018Review
- Effects of Early-Life Stress on Social and Anxiety-Like Behaviors in Adult Mice: Sex-Specific Effects.Behavioural neurology · 2018Article
- Phenotypic outcomes in adolescence and adulthood in the scarcity-adversity model of low nesting resources outside the home cage.Developmental psychobiology · 2017Article
- Insight from animal models of environmentally driven epigenetic changes in the developing and adult brain.Development and psychopathology · 2016Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.