PMID- 22582138
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Print)
IS  - 1948-7193 (Linking)
VI  - 3
IP  - 1
DP  - 2012 Jan 18
TI  - Neonatal citalopram treatment inhibits the 5-HT depleting effects of MDMA 
      exposure in rats.
PG  - 12-21
AB  - Neonatal exposure to 3,4-methylenedioxymethamphetamine (MDMA) produces long-term 
      learning and memory deficits and increased anxiety-like behavior. The mechanism 
      underlying these behavioral changes is unknown but we hypothesized that it 
      involves perturbations to the serotonergic system as this is the principle mode 
      of action of MDMA in the adult brain. During development 5-HT is a neurotrophic 
      factor involved in neurogenesis, synaptogenesis, migration, and target region 
      specification. We have previously showed that MDMA exposure (4x10 mg/kg/day) from 
      P11-20 (analogous to human third trimester exposure) induces ~50% decreases in 
      hippocampal 5-HT throughout treatment. To determine whether MDMA-induced 5-HT 
      changes are determinative, we tested if these changes could be prevented by 
      treatment with a selective serotonin reuptake inhibitor (citalopram: CIT). In a 
      series of experiments we evaluated the effects of different doses and dose 
      regimens of CIT on MDMA-induced 5-HT depletions in three brain regions 
      (hippocampus, entorhinal cortex, and neostriatum) at three time-points (P12, P16, 
      P21) during the treatment interval (P11-20) known to induce behavioral 
      alterations when animals are tested as adults. We found that 5 mg/kg CIT 
      administered twice daily significantly attenuated MDMA-induced 5-HT depletions in 
      all three regions at all three ages but that the protection was not complete at 
      all ages. Striatal dopamine was unaffected. We also found increases in 
      hippocampal NGF and plasma corticosterone following MDMA treatment on P16 and 
      P21, respectively. No changes in BDNF were observed. CIT treatment may be a 
      useful means of interfering with MDMA-induced 5-HT reductions and thus permit 
      tests of the hypothesis that the drug's cognitive and/or anxiety effects are 
      mediated through early disruptions to 5-HT dependent developmental processes.
FAU - Schaefer, Tori L
AU  - Schaefer TL
AD  - Division of Neurology, Dept. of Pediatrics, Cincinnati Children's Research 
      Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 
      45229-3039, USA.
FAU - Grace, Curtis E
AU  - Grace CE
FAU - Skelton, Matthew R
AU  - Skelton MR
FAU - Graham, Devon L
AU  - Graham DL
FAU - Gudelsky, Gary A
AU  - Gudelsky GA
FAU - Vorhees, Charles V
AU  - Vorhees CV
FAU - Williams, Michael T
AU  - Williams MT
LA  - eng
GR  - R01 DA007427-16/DA/NIDA NIH HHS/United States
GR  - T32 ES007051/ES/NIEHS NIH HHS/United States
GR  - R01 DA006733-12/DA/NIDA NIH HHS/United States
GR  - T32 ES007051-35/ES/NIEHS NIH HHS/United States
GR  - R01 DA006733/DA/NIDA NIH HHS/United States
GR  - R01 DA007427/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20111021
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
PMC - PMC3347712
MID - NIHMS336341
EDAT- 2012/05/15 06:00
MHDA- 2012/05/15 06:01
PMCR- 2013/01/18
CRDT- 2012/05/15 06:00
PHST- 2012/05/15 06:00 [entrez]
PHST- 2012/05/15 06:00 [pubmed]
PHST- 2012/05/15 06:01 [medline]
PHST- 2013/01/18 00:00 [pmc-release]
AID - 10.1021/cn2000553 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2012 Jan 18;3(1):12-21. doi: 10.1021/cn2000553. Epub 2011 Oct 
      21.