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Article

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Accepted version

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2014-06-28

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/65528

3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility

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http://dx.doi.org/10.1016/j.pnpbp.2014.06.007

Abstract

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 30 mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3 h), on 1 day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30 mg/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
50 μM) for 6 or 48 h significantly increased basal Ca2 +, 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.

Subject

Al·lucinògens, Amfetamines, Compostos heterocíclics, Epilèpsia, Neurotoxicologia, Ratolins (Animals de laboratori), Sistema nerviós central

Subject (English)

Hallucinogenic drugs, Amphetamines, Heterocyclic compounds, Epilepsy, Neurotoxicology, Mice (Laboratory animals), Central nervous system

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citation

ABAD, Sonia, et al. 3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2014. Vol. 54, num. 231-242. ISSN 0278-5846. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/65528

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