PMID- 24977329
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20140816
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 54
DP  - 2014 Oct 3
TI  - 3,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibility.
PG  - 231-42
LID - S0278-5846(14)00126-2 [pii]
LID - 10.1016/j.pnpbp.2014.06.007 [doi]
AB  - 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 (10-50muM) 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Abad, Sonia
AU  - Abad S
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      University of Barcelona, Barcelona, Spain.
FAU - Junyent, Felix
AU  - Junyent F
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      University of Barcelona, Barcelona, Spain.
FAU - Auladell, Carme
AU  - Auladell C
AD  - 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.
FAU - Pubill, David
AU  - Pubill D
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      University of Barcelona, Barcelona, Spain.
FAU - Pallas, Merce
AU  - Pallas M
AD  - 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.
FAU - Camarasa, Jorge
AU  - Camarasa J
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      University of Barcelona, Barcelona, Spain.
FAU - Escubedo, Elena
AU  - Escubedo E
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      University of Barcelona, Barcelona, Spain. Electronic address: eescubedo@ub.edu.
FAU - Camins, Antonio
AU  - Camins A
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140628
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Convulsants)
RN  - 0 (Hallucinogens)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - SIV03811UC (Kainic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/pathology/physiology
MH  - Calcium/metabolism
MH  - Cell Death/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/pathology/physiopathology
MH  - Convulsants/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Gliosis/chemically induced/pathology/physiopathology
MH  - Hallucinogens/administration & dosage/*toxicity
MH  - Hippocampus/drug effects/growth & development/pathology/physiopathology
MH  - Kainic Acid/*toxicity
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Microglia/drug effects/pathology/physiology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Neurons/drug effects/pathology/physiology
MH  - Random Allocation
MH  - Seizures/*chemically induced/pathology/physiopathology
OTO - NOTNLM
OT  - Calbindin
OT  - Calretinin
OT  - Kainic acid
OT  - MDMA
OT  - Parvalbumin
OT  - Seizures
EDAT- 2014/07/01 06:00
MHDA- 2015/05/13 06:00
CRDT- 2014/07/01 06:00
PHST- 2014/03/24 00:00 [received]
PHST- 2014/05/27 00:00 [revised]
PHST- 2014/06/11 00:00 [accepted]
PHST- 2014/07/01 06:00 [entrez]
PHST- 2014/07/01 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - S0278-5846(14)00126-2 [pii]
AID - 10.1016/j.pnpbp.2014.06.007 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:231-42. doi: 
      10.1016/j.pnpbp.2014.06.007. Epub 2014 Jun 28.