Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System
Terrell Holloway, José L. Moreno, Adrienne Umali, Vinayak Rayannavar, Georgia E. Hodes, Scott J. Russo, Javier González-Maeso
Journal of Neuroscience January 16, 2013 DOI: 10.1523/jneurosci.2331-12.2013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | maternal variable stress |
| Topics | Serotonin |
| Keywords | Offspring Metabotropic receptor Metabotropic glutamate receptor Pregnancy Agonist Schizophrenia object-oriented programming Endocrinology Prenatal stress |
| Citations | 122 |
| Key findings | Prenatal stress increased 5-HT2A and decreased mGlu2 receptor expression in the frontal cortex, with corresponding behavioral changes in adult but not prepubertal mice. |
Abstract
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT 2A and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT 2A and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition, and mood. This pattern of expression of 5-HT 2A and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT 2A agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 (1 R ,4 R ,5 S ,6 R -2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not attributable to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with polyinosinic:polycytidylic acid [poly(I:C)] during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.
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 7
- Serotonin 2A receptors are a stress response system: implications for post-traumatic stress disorder. Behavioural Pharmacology April 1, 2019
- Serotonergic hallucinogens as translational models relevant to schizophrenia The International Journal of Neuropsychopharmacology August 13, 2013
- Differences across sexes on head-twitch behavior and 5-HT2A receptor signaling in C57BL/6J mice. Neuroscience Letters September 25, 2022
- Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice The International Journal of Neuropsychopharmacology April 24, 2014
- Preclinical models of antipsychotic drug action The International Journal of Neuropsychopharmacology June 10, 2013
and 2 more in the library
Cites 7
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Maternal Influenza Viral Infection Causes Schizophrenia-Like Alterations of 5-HT 2A and mGlu 2 Receptors in the Adult Offspring Journal of Neuroscience February 2, 2011
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
- Psychedelics and schizophrenia. Trends in Neurosciences April 1, 2009
and 2 more in the library