3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility.
Sonia Abad, Fèlix Junyent, Carme Auladell, David Pubill, Mercè Pallàs, Jorge Camarasa, Elena Escubedo, Antonio Camins
Progress in Neuro-Psychopharmacology and Biological Psychiatry October 3, 2014 DOI: 10.1016/j.pnpbp.2014.06.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent male C57BL/6 mice |
| Interventions | MDMA Kainic acid |
| Dose | MDMA 10-50 micromolar (cortical neurons); kainic acid 20 or 30 mg/kg |
| Duration | MDMA three times daily (every 3 hours) one day per week for 4 consecutive weeks; kainic acid injected 24 hours after last MDMA; cortical neurons treated for 6 or 48 hours |
| Measures | Fluoro-Jade staining, parvalbumin, calbindin, calretinin, basal Ca(2+), basal Na(+) |
| Topics | MDMA |
| Keywords | Calbindin Calretinin Kainic acid Parvalbumin Seizures |
| Key findings | MDMA pretreatment increased susceptibility to kainic acid-induced seizures and potentiated kainic acid-induced neurodegeneration, including more Fluoro-Jade-positive cells in CA1 and greater parvalbumin loss in CA1 and dentate gyrus. MDMA alone caused no neuronal damage but transiently reduced calbindin and calretinin. In cortical neurons, MDMA increased basal calcium, reduced basal sodium, and potentiated kainate responses. The authors propose these effects involve disrupted intracellular ionic homeostasis or indirect glutamate release. |
Abstract
Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3h), on 1day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30mg/kg). After this injection, we evaluated seizures, hippocampal neuronal cell death, microgliosis, astrogliosis, and calcium binding proteins. MDMA pretreatment, by itself, did not induce neuronal damage but increased seizure susceptibility in all KA treatments and potentiated the presence of Fluoro-Jade-positive cells in CA1. Furthermore, MDMA, like KA, significantly decreased parvalbumin levels in CA1 and dentate gyrus, where it potentiated the effects of KA. The amphetamine derivative also promoted a transient decrease in calbindin and calretinin levels, indicative of an abnormal neuronal discharge. In addition, treatment of cortical neurons with MDMA (10-50μM) for 6 or 48h significantly increased basal Ca(2+), reduced basal Na(+) levels and potentiated kainate response. These results indicate that MDMA potentiates KA-induced neurodegeneration and also increases KA seizure susceptibility. The mechanism proposed includes changes in Calcium Binding Proteins expression, probably due to the disruption of intracellular ionic homeostasis, or/and an indirect effect through glutamate release.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Progression and Persistence of Neurotoxicity Induced by MDMA in Dopaminergic Regions of the Mouse Brain and Association with Noradrenergic, GABAergic, and Serotonergic Damage. Neurotoxicity Research November 2017
- Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits. Molecular Neurobiology December 2016
- MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate. Neurotoxicology December 2016
- 3,4‐methylenedioxymethamphetamine increases excitability in the dentate gyrus: role of 5HT2A receptor‐inducedPGE2 signaling Journal of Neurochemistry March 1, 2016
and 1 more in the library
Cites 9
- A study of the mechanisms involved in the neurotoxic action of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain British Journal of Pharmacology December 1, 2001
- 3,4‐methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein Synapse July 14, 2004
- Effect of Repeated (‘Binge’) Dosing of MDMA to Rats Housed at Normal and High Temperature on Neurotoxicdamage to Cerebral 5-Ht and Dopamine Neurones Journal of Psychopharmacology September 1, 2004
- MDMA‐induced neurotoxicity: long‐term effects on 5‐HT biosynthesis and the influence of ambient temperature British Journal of Pharmacology June 12, 2006
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
and 4 more in the library