title: 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: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain.
authors: Sónia
authors: S
authors: Abad
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain.
authors: Fèlix
authors: F
authors: Junyent
authors: Department of Cellular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors: Carme
authors: C
authors: Auladell
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain.
authors: David
authors: D
authors: Pubill
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors: Mercè
authors: M
authors: Pallàs
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain.
authors: Jorge
authors: J
authors: Camarasa
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain. Electronic address: eescubedo@ub.edu.
authors: Elena
authors: E
authors: Escubedo
authors: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Barcelona, Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
authors: Antonio
authors: A
authors: Camins
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003292:Convulsants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: D003292:Convulsants; D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D007608:Kainic Acid; D002118:Calcium
keywords: Calbindin; Calretinin; Kainic acid; MDMA; Parvalbumin; Seizures