Early emergence of altered 5-HT2A receptor-evoked behavior, neural activation and gene expression following maternal separation.
Ankit Sood, Sthitapranjya Pati, Amrita Bhattacharya, Karina Chaudhari, Vidita A Vaidya
International Journal of Developmental Neuroscience April 2018 DOI: 10.1016/j.ijdevneu.2017.10.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rat pups at postnatal day 21, either maternally separated or control |
| Interventions | DOI (1-(2 5-dimethoxy-4-iodophenyl)-2-aminopropane) Maternal separation |
| Dose | 2 mg/kg |
| Duration | Maternal separation 3 h daily from postnatal day 2 to 14; assessment at postnatal day 21 |
| Measures | head-twitch behavior, c-Fos cell counting, immediate early gene mRNA profiling (Fos, Fra1, Bdnf, Egr1, Egr3) |
| Topics | Serotonin |
| Keywords | Early stress Head twitch behavior Immediate early gene C-fos Mpfc |
| Key findings | Maternally separated rat pups at postnatal day 21 showed enhanced DOI-evoked head-twitch behavior and altered DOI-evoked c-Fos expression in all medial prefrontal cortex subdivisions but not in hippocampus, lateral septum, or hypothalamus. Baseline Fos, Fra1, and Egr1 mRNA was lower in the medial prefrontal cortex of separated pups, and DOI regulation of several immediate early genes differed, suggesting early emergence of altered 5-HT2A receptor function after maternal separation. |
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-HT2A receptor function in adulthood. However, the ontogeny of altered 5-HT2A receptor responsivity following MS remains unknown. Here, we examined 5-HT2A receptor agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (2mg/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 3h 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-HT2A receptor stimulation following early stress. Gene profiling of 5-HT2A receptor-regulated immediate early genes (IEGs) indicated a decline in the expression of Fos, Fra1 and Egr1 mRNA under baseline conditions in the mPFC of MS pups. MS pups also showed an altered pattern in the regulation of several 5-HT2A receptor-regulated IEGs (Fos, Fra1, Bdnf, Egr1, Egr3) following DOI treatment. Collectively, these results highlight an early emergence of altered 5-HT2A receptor-evoked behavioral responses and neural activation patterns in multiple brain regions in animals with a history of MS.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 5
- Pivotal mental states Journal of Psychopharmacology April 1, 2021
- Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder. Behavioural Pharmacology April 1, 2019
- A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex. Brain 2024
- Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice International Journal of Molecular Sciences December 4, 2022
- Cellular mechanisms of serotonergic psychedelics - apical hypercontextualisation. Neuroscience & Biobehavioral Reviews July 1, 2026
Cites 9
- Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism Journal of Neuroscience December 15, 2001
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons Journal of Neuroscience December 1, 2000
- Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System Journal of Neuroscience January 16, 2013
- Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice The International Journal of Neuropsychopharmacology April 24, 2014
and 4 more in the library