3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility.

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.

• Authors: Sónia Abad, Fèlix Junyent, Carme Auladell, David Pubill, Mercè Pallàs, Jorge Camarasa, Elena Escubedo, Antonio Camins
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 54 Pg. 231-42 (Oct 03 2014) ISSN: 1878-4216 [Electronic] England
• PMID: 24977329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Convulsants
• Hallucinogens
• N-Methyl-3,4-methylenedioxyamphetamine
• Kainic Acid
• Calcium

Topics

• Animals
• Astrocytes (drug effects, pathology, physiology)
• Calcium (metabolism)
• Cell Death (drug effects)
• Cells, Cultured
• Cerebral Cortex (drug effects, pathology, physiopathology)
• Convulsants (toxicity)
• Dose-Response Relationship, Drug
• Gliosis (chemically induced, pathology, physiopathology)
• Hallucinogens (administration & dosage, toxicity)
• Hippocampus (drug effects, growth & development, pathology, physiopathology)
• Kainic Acid (toxicity)
• Male
• Mice, Inbred C57BL
• Microglia (drug effects, pathology, physiology)
• N-Methyl-3,4-methylenedioxyamphetamine (administration & dosage, toxicity)
• Neurons (drug effects, pathology, physiology)
• Random Allocation
• Seizures (chemically induced, pathology, physiopathology)