PMID- 20477949
OWN - NLM
STAT- MEDLINE
DCOM- 20101006
LR  - 20151119
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 114
IP  - 3
DP  - 2010 Aug
TI  - Delayed pre-conditioning by 3-nitropropionic acid prevents 
      3,4-methylenedioxymetamphetamine-induced 5-HT deficits.
PG  - 843-52
LID - 10.1111/j.1471-4159.2010.06808.x [doi]
AB  - The aim of the present study was to investigate whether late pre-conditioning 
      using 3-nitropropionic acid (3NP) prevents the 5-hydroxytryptamine (5-HT) 
      deficits caused by the amphetamine derivative 3,4-methylenedioxymethamphetamine 
      (MDMA) in the rat. For this purpose we administered 3NP 24 h before MDMA (3 x 5 
      mg/kg i.p., every 2 h) and rats were killed 7 days later. Pre-treatment of 3NP 
      afforded complete protection against MDMA-induced 5-HT deficits independent of 
      any effect on MDMA-induced hyperthermia or 5-HT transporter activity. To identify 
      the transductional mechanisms responsible for the neuroprotective effect of 3NP, 
      we first examined the involvement of nitric oxide (NO) by using selective 
      inhibitors of all three nitric oxide synthase isoforms. Inhibition of endothelial 
      and neuronal nitric oxide synthase, but not inducible nitric oxide synthase, 
      reversed 3NP-induced pre-conditioning. The NO donor 
      S-Nitroso-N-acetylpenicilamine mimicked 3NP effects further suggesting the 
      involvement of NO in mediating 3NP protection. To investigate the involvement of 
      NOS/soluble guanylate cyclase (sGC)/protein kinase G/mitochondrial ATP-sensitive 
      potassium channels (mitoK(ATP)) signaling pathway we examined the effect of 
      5-hydroxydecanoate (5-HD), a selective mitoK(ATP) blocker, and 
      1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one, a potent inhibitor of sGC, on 
      3NP-induced tolerance. 5-hydroxydecanoate, but not 
      1H-(1,2,4)oxadiazolo[4,3-a]quinoxaline-1-one, suppressed 3NP-mediated protection 
      suggesting that mitoK(ATP) opening, but not NO-mediated activation of sGC, 
      participates in the mechanism underlying tolerance to MDMA. Our data also showed 
      that the protective effect of 3NP was abolished by cycloheximide, supporting the 
      involvement of de novo protein synthesis. In conclusion, 3NP-induced delayed 
      tolerance against 5-HT deficits caused by MDMA occurs via NO production.
FAU - Puerta, Elena
AU  - Puerta E
AD  - Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, 
      Spain.
FAU - Pastor, Fiona
AU  - Pastor F
FAU - Dvoracek, Jan
AU  - Dvoracek J
FAU - de Saavedra, Maria D M
AU  - de Saavedra MD
FAU - Goni-Allo, Beatriz
AU  - Goni-Allo B
FAU - Jordan, Joaquin
AU  - Jordan J
FAU - Hervias, Isabel
AU  - Hervias I
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100513
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Nitro Compounds)
RN  - 0 (Propionates)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Serotonin Agents)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - QY4L0FOX0D (3-nitropropionic acid)
SB  - IM
MH  - Animals
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - Neuroprotective Agents/administration & dosage/*pharmacology
MH  - Nitric Oxide/biosynthesis/physiology
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitric Oxide Synthase/antagonists & inhibitors/metabolism
MH  - Nitro Compounds/administration & dosage/*pharmacology
MH  - Propionates/administration & dosage/*pharmacology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*deficiency/toxicity
MH  - Serotonin Agents/administration & dosage/pharmacology
EDAT- 2010/05/19 06:00
MHDA- 2010/10/07 06:00
CRDT- 2010/05/19 06:00
PHST- 2010/05/19 06:00 [entrez]
PHST- 2010/05/19 06:00 [pubmed]
PHST- 2010/10/07 06:00 [medline]
AID - JNC6808 [pii]
AID - 10.1111/j.1471-4159.2010.06808.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Aug;114(3):843-52. doi: 10.1111/j.1471-4159.2010.06808.x. Epub 
      2010 May 13.