PMID- 21948520
OWN - NLM
STAT- MEDLINE
DCOM- 20120823
LR  - 20151119
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 90
IP  - 2
DP  - 2012 Feb
TI  - Long-lasting neuroprotective effect of sildenafil against 
      3,4-methylenedioxymethamphetamine- induced 5-hydroxytryptamine deficits in the 
      rat brain.
PG  - 518-28
LID - 10.1002/jnr.22759 [doi]
AB  - Sildenafil, given shortly before 3,4-methylenedioxymethamphetamine (MDMA), 
      affords protection against 5-hydroxytryptamine (5-HT) depletions caused by this 
      amphetamine derivative by an acute preconditioning-like mechanism. Because acute 
      and delayed preconditionings do not share the same mechanisms, we investigated 
      whether sildenafil would also protect the 5-HT system of the rat if given 24 hr 
      before MDMA. For this, MDMA (3 x 5 mg/kg i.p., every 2 hr) was administered to 
      rats previously treated with sildenafil (8 mg/kg p.o.). One week later, 5-HT 
      content and 5-HT transporter density were measured in the striatum, frontal 
      cortex, and hippocampus of the rats. Our findings indicate that sildenafil 
      afforded significant protection against MDMA-induced 5-HT deficits without 
      altering the acute hyperthermic response to MDMA or its metabolic disposition. 
      Sildenafil promoted ERK1/2 activation an effect that was paralleled by an 
      increase in MnSOD expression that persisted 24 hr later. In addition, superoxide 
      and superoxide-derived oxidants, shown by ethidium fluorescence, increased after 
      the last MDMA injection, an effect that was prevented by sildenafil pretreatment. 
      Similarly, MDMA increased nitrotyrosine concentration in the hippocampus, an 
      effect not shown by sildenafil-pretreated rats. In conclusion, our data 
      demonstrate that sildenafil produces a significant, long-lasting neuroprotective 
      effect against MDMA-induced 5-HT deficits. This effect is apparently mediated by 
      an increased expression of MnSOD and a subsequent reduced susceptibility to the 
      oxidative stress caused by MDMA.
CI  - Copyright (c) 2011 Wiley Periodicals, Inc.
FAU - Puerta, Elena
AU  - Puerta E
AD  - Department of Pharmacology, School of Pharmacy, University of Navarra, Pamplona, 
      Spain.
FAU - Barros-Minones, Lucia
AU  - Barros-Minones L
FAU - Hervias, Isabel
AU  - Hervias I
FAU - Gomez-Rodriguez, Violeta
AU  - Gomez-Rodriguez V
FAU - Orejana, Lourdes
AU  - Orejana L
FAU - Pizarro, Neus
AU  - Pizarro N
FAU - de la Torre, Rafael
AU  - de la Torre R
FAU - Jordan, Joaquin
AU  - Jordan J
FAU - Aguirre, Norberto
AU  - Aguirre N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110921
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - 333DO1RDJY (Serotonin)
RN  - BW9B0ZE037 (Sildenafil Citrate)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism/*pathology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/antagonists & inhibitors/*toxicity
MH  - Neuroprotective Agents/*administration & dosage
MH  - Piperazines/*administration & dosage
MH  - Purines/administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Serotonin/*deficiency/metabolism
MH  - Sildenafil Citrate
MH  - Sulfones/*administration & dosage
MH  - Time Factors
EDAT- 2011/09/29 06:00
MHDA- 2012/08/24 06:00
CRDT- 2011/09/28 06:00
PHST- 2011/04/12 00:00 [received]
PHST- 2011/06/14 00:00 [revised]
PHST- 2011/07/03 00:00 [accepted]
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/08/24 06:00 [medline]
AID - 10.1002/jnr.22759 [doi]
PST - ppublish
SO  - J Neurosci Res. 2012 Feb;90(2):518-28. doi: 10.1002/jnr.22759. Epub 2011 Sep 21.