In utero exposure to dexamethasone causes a persistent and age-dependent exacerbation of the neurotoxic effects and glia activation induced by MDMA in dopaminergic brain regions of C57BL/6J mice.
Giulia Costa, Stefan Spulber, Elena Paci, Maria Antonietta Casu, Sandra Ceccatelli, Nicola Simola, Micaela Morelli
Neurotoxicology March 2021 Retracted DOI: 10.1016/j.neuro.2020.12.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Pregnant C57BL6/J mice and their male offspring |
| Interventions | Dexamethasone 3 |
| Dose | Dexamethasone 0.05 mg/kg per day; MDMA 4 × 20 mg/kg, 2 h apart |
| Duration | Dexamethasone from gestational day 14 until delivery; MDMA administered at adolescence or adulthood, with sacrifice 48 h later |
| Measures | Tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (IBA-1), interleukin-1β (IL-1β), interleukin-10 (IL-10) |
| Topics | MDMA |
| Keywords | Adolescence Amphetamine-related drugs Tyrosine hydroxylase |
| Key findings | Prenatal dexamethasone exposure followed by later MDMA treatment produced greater loss of dopaminergic neurons in the substantia nigra of adolescent mice and greater astrogliosis in adolescent and adult mice than in controls. The authors suggest prenatal glucocorticoid exposure may cause an age-dependent, persistent increase in susceptibility to central toxicity from amphetamine-related drugs used later in life. |
Abstract
Clinical and preclinical evidence indicates that prenatal exposure to glucocorticoids may induce detrimental effects in the offspring, including reduction in fetal growth and alterations in the CNS. On this basis, the present study investigated whether in utero exposure to high levels of glucocorticoids is a risk factor that may lead to an exacerbation of the central noxious effects induced by psychoactive drugs consumed later in life. To this end, pregnant C57BL6/J dams were treated with dexamethasone (DEX, 0.05 mg/kg per day) from gestational day 14 until delivery. Thereafter, the male offspring were evaluated to ascertain the magnitude of dopaminergic damage, astrogliosis and microgliosis elicited in the nigrostriatal tract by the amphetamine-related drug 3,4--methylenedioxymethamphetamine (MDMA, 4 × 20 mg/kg, 2 h apart, sacrificed 48 h later) administered at either adolescence or adulthood. Immunohistochemistry was performed in the substantia nigra pars compacta (SNc) and striatum, to evaluate dopaminergic degeneration by measuring tyrosine hydroxylase (TH), as well as astrogliosis and microgliosis by measuring glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1), respectively. Moreover, immunohistochemistry was used to ascertain the co-localization of IBA-1 with either the pro-inflammatory interleukin (IL) IL-1β or the anti-inflammatory IL IL-10, in order to determine the microglial phenotype. In utero administration of DEX induced dopaminergic damage by decreasing the density of TH-positive fibers in the striatum, although only in adult mice. MDMA administration induced dopaminergic damage and glia activation in the nigrostriatal tract of adolescent and adult mice. Mice exposed to DEX in utero and treated with MDMA later in life showed a more pronounced loss of dopaminergic neurons (adolescent mice) and astrogliosis (adolescent and adult mice) in the SNc, compared with control mice. These results suggest that prenatal exposure to glucocorticoids may induce an age-dependent and persistent increase in the susceptibility to central toxicity of amphetamine-related drugs used later in life.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 4
- Neurotoxicity of MDMA: Main effects and mechanisms. Experimental Neurology October 1, 2021
- Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie May 1, 2023
- The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research Behavioural Brain Research February 10, 2026
- The Potential Neuroinflammatory Attenuation Effects of Thymoquinone against 3, 4-Methylenedioxymethamphetamine-Induced Microglial Activation in BV2 Mouse Cell Line bioRxiv Preprint Server June 16, 2025
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and 13 more in the library