Effect of 5-HT depletion by MDMA on hyperthermia and Arc mRNA induction in rat brain.
Thomas J R Beveridge, Annis O. Mechan, Marie Sprakes, Qi Pei, Tyra S C Zetterstrom, Alfred Richard Green, J Martin Elliott
Psychopharmacology May 2004 DOI: 10.1007/s00213-003-1753-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Duration | 21 days after neurotoxic dose |
| Measures | Arc mRNA expression, brain 5-HT and 5-HIAA levels |
| Topics | MDMA Serotonin |
| Key findings | MDMA-induced hyperthermia and Arc mRNA expression were unaffected by moderate serotonin depletion, questioning serotonergic mediation. After a neurotoxic dose, basal Arc expression increased in cortex and CA1, suggesting altered synaptic plasticity. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) administration to rats produces an acute hyperthermic response and induces localised neuronal activation, which can be visualised via expression of immediate-early genes. The pharmacological and anatomical basis of these effects are unclear. At high doses, MDMA also causes selective neurotoxicity at serotonergic nerve terminals. We investigated the effect of 5-hydroxytryptamine (5-HT) depletion on the acute hyperthermic response to MDMA and the pattern of neuronal excitation indicated by Arc (activity-regulated cytoskeleton associated gene) in naive rats and following administration of MDMA at a neurotoxic dose. Expression of Arc mRNA was investigated by in situ hybridisation histochemistry using 35S-labelled oligonucleotide probe. MDMA induced a significant hyperthermia together with increased Arc mRNA expression in cortical regions, caudate-putamen and CA1 hippocampus but not hypothalamus. At 21 days after a neurotoxic dose of MDMA, brain 5-HT and 5-HIAA levels were significantly reduced by 21-32%. In these animals, both the hyperthermic response and the pattern and extent of Arc mRNA expression induced by a subsequent dose of MDMA were unaltered. However, basal Arc expression was significantly increased in cortical regions and CA1 hippocampus. We conclude that the acute hyperthermic response induced by MDMA is not attenuated by moderate depletion of 5-HT, further questioning mediation via a serotonergic mechanism. Arc mRNA induction by MDMA exhibits highly localised expression, which is not altered following 5-HT depletion. However, following a neurotoxic dose of MDMA, basal expression of Arc is increased, particularly in cortex and CA1, suggesting that mechanisms underlying synaptic plasticity might also be modified.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- Ultrastructural characterization of tryptophan hydroxylase 2-specific cortical serotonergic fibers and dorsal raphe neuronal cell bodies after MDMA treatment in rat. Psychopharmacology February 2011
- Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects. Psychopharmacology March 2008
- Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. Psychopharmacology July 2007
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