Early emergence of altered 5‐HT2Areceptor‐evoked behavior, neural activation and gene expression following maternal separation
Abstract
Abstract The early stress of Maternal Separation (MS) contributes to the establishment of adult psychopathology. The serotonergic (5‐HT) system is implicated during this temporal window in mediating the development of mood‐related behaviors. MS is reported to evoke altered 5‐HT2Areceptor function in adulthood. However, the ontogeny of altered 5‐HT2Areceptor responsivity following MS remains unknown. Here, we examined 5‐HT2Areceptor agonist, DOI (1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane) (2 mg/kg) evoked responses, namely stereotypical head‐twitch behaviors in control and MS Sprague‐Dawley rat pups at postnatal day 21 (P21). MS involved a separation of pups from the dam for 3 h daily from postnatal day 2–14. MS pups at P21 exhibited significantly enhanced head‐twitch behaviors compared to controls. Using c‐Fos cell counting we examined neural activation in control and MS pups following DOI treatment. MS pups exhibited altered DOI‐evoked c‐Fos expression within all mPFC subdivisions, but not in the hippocampus, lateral septum and hypothalamus, suggesting differential prefrontal neural activation upon 5‐HT2Areceptor stimulation following early stress. Gene profiling of 5‐HT2Areceptor‐regulated immediate early genes (IEGs) indicated a decline in the expression ofFos,Fra1andEgr1mRNA under baseline conditions in the mPFC of MS pups. MS pups also showed an altered pattern in the regulation of several 5‐HT2Areceptor‐regulated IEGs (Fos,Fra1,Bdnf,Egr1,Egr3) following DOI treatment. Collectively, these results highlight an early emergence of altered 5‐HT2Areceptor‐evoked behavioral responses and neural activation patterns in multiple brain regions in animals with a history of MS.
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Pre-gestational and early-life stress with HPA activation is linked to an altered serotonergic system, leading to interruptions in brain development and cognition.
“Pre-gestational and early-life stress, with activation of the HPA axis, have been linked with an altered serotonergic system, leading to interruptions in brain development and cognition (218–220).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [219]
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- Authors
- Sood, A., Pati, S., Bhattacharya, A., Chaudhari, K., & Vaidya, V. A.
- Affiliations
- Tata Institute of Fundamental Research (IN)
- Corresponding author
- Vaidya, Vidita A.
- Venue
- International Journal of Developmental Neuroscience
- Publisher
- Wiley
- Published
- 2017-10-14
- Volume
- 65
- Issue
- 1
- Pages
- 21-28
- ISSN
- 0736-5748 (ISSN-L)
- 1873-474X
- OpenAlex
- W2764323190
- Cited by
- 25
- References
- 52
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 1
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- TIFR
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- maternal separation, early life stress, 5-HT2A receptor, serotonin, digital object identifiers, c-fos, medial prefrontal cortex, immediate early genes, FOS, Fra-1, EGR1, brain-derived neurotrophic factor, ontogeny
- MeSH terms
- Age Factors, Amphetamines, Animals, Animals, Newborn, Behavior, Animal, Brain, Female, Humans, Male, Maternal Deprivation, Neurons, RNA, Messenger, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Immediate-Early Proteins, Gene Expression Regulation, Developmental, Receptor, Serotonin, 5-HT2A, Rats
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