Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion.
Rómeó D. Andó, Csaba Ádori, Eszter Kirilly, Eszter Molnár, Gábor G. Kovács, Linda Ferrington, Paul A. Kelly, György Bagdy
Behavioural Brain Research March 5, 2010 DOI: 10.1016/j.bbr.2009.10.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Dark Agouti rats |
| Interventions | MDMA fluoxetine meta-chloro-phenylpiperazine (m-CPP) citalopram |
| Dose | MDMA 15 or 30 mg/kg, i.p. |
| Duration | 6 months after MDMA treatment |
| Measures | social interaction test, serotonin-transporter immunohistochemistry, tryptophan-hydroxylase immunohistochemistry, 2-deoxyglucose autoradiographic imaging |
| Topics | MDMA |
| Key findings | Six months after a single MDMA dose (15 or 30 mg/kg), serotonergic axon densities in rats had recovered in most brain areas but remained reduced in hippocampus and thalamus. The acute anxiogenic effect of fluoxetine, but not m-CPP, was attenuated in MDMA-pretreated animals, and metabolic responses to citalopram and fluoxetine were attenuated only in ventromedial thalamus and hippocampal subfields, suggesting that some serotonergic functions remain altered despite axonal recovery. |
Abstract
To assess the functional state of the serotonergic system, the acute behavioural and brain metabolic effect of SSRI antidepressants were studied during the recovery period after MDMA-induced neuronal damage. The effects of the SSRI fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m-CPP) were investigated in the social interaction test in Dark Agouti rats, 6 months after treatment with a single dose of MDMA (15 or 30 mg kg(-1), i.p.). At earlier time points these doses of MDMA have been shown to cause 30-60% loss in axonal densities in several brain regions. Densities of the serotonergic axons were assessed using serotonin-transporter and tryptophan-hydroxylase immunohistochemistry. In a parallel group of animals, brain function was examined following an acute challenge with either fluoxetine or citalopram, using 2-deoxyglucose autoradiographic imaging. Six months after MDMA treatment the densities of serotonergic axons were decreased in only a few brain areas including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were attenuated in animals pretreated with MDMA. The metabolic response to both citalopram and fluoxetine was normal in most of the brain areas examined with the exception of ventromedial thalamus and hippocampal sub-fields where the response was attenuated. These data provide evidence that 6 months after MDMA-induced damage serotonergic axons show recovery in most brain areas, but serotonergic functions to challenges with SSRIs including anxiety and aggression remain altered.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- A Systematic Review of the MDMA Model to Address Social Impairment in Autism. Current Neuropharmacology 2021
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- Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: Temporal, spatial, and cellular patterns The Journal of Comparative Neurology 2006
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