A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.
Laura Orío, Noemi Llopis, Elisa Torres, Maria Izco, Esther O'Shea, María Isabel Colado
Neurotoxicity Research August 2010 DOI: 10.1007/s12640-009-9120-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adult male Dark Agouti rats |
| Interventions | Minocycline MDMA |
| Dose | Minocycline 45 mg/kg on the first day and 90 mg/kg on the second day, twice a day 12 h apart, i.p.; MDMA 12.5 mg/kg, i.p. |
| Duration | Minocycline given for 2 days; assessments at 1 h, 3 h, 24 h, and 7 days after MDMA |
| Measures | NFkappaB binding activity, IL-1beta, microglial activation, [(3)H]-paroxetine binding |
| Topics | MDMA Serotonin |
| Key findings | MDMA increased NFkappaB activation, IL-1beta release, microglial activation, and 5-HT neurotoxicity in rat frontal cortex and hypothalamus. Minocycline prevented all these effects in frontal cortex but, in hypothalamus, prevented only microglial activation, not NFkappaB activation, IL-1beta release, or neurotoxicity. The authors suggest minocycline's frontal cortex protection involves inhibition of MDMA-induced NFkappaB activation, possibly via reduced IL-1beta signalling. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
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- Methylenedioxymethamphetamine (‘Ecstasy’)‐induced immunosuppression: a cause for concern? British Journal of Pharmacology May 27, 2010
- Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA): regulation by CB2 receptors and implications for neurotoxicity Journal of Neuroinflammation August 6, 2011
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics. Neurochemical Research April 1, 2023
- The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa Scientific Reports March 13, 2019
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