PMID- 12429568
OWN - NLM
STAT- MEDLINE
DCOM- 20030520
LR  - 20231105
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 137
IP  - 7
DP  - 2002 Dec
TI  - Functional consequences of perinatal exposure to 
      3,4-methylenedioxymethamphetamine in rat brain.
PG  - 963-70
AB  - 1. In this study we have examined methylenedioxymethamphetamine (MDMA)-induced 
      toxicity in perinatal rat brain, related this to normal development of serotonin 
      transporter sites (SERT), and determined whether early exposure to MDMA 
      subsequently alters cerebral function in adults. 2. Perinatal development of SERT 
      was visualized and quantified using [(3)H]-paroxetine binding autoradiography in 
      embryonic and neonatal rat brain from embryonic day 15 (E15) to postnatal day p30 
      (p30). Cerebral glucose utilization (lCMR(glu)) was measured by 2-deoxyglucose 
      autoradiography in adult rats. 3. [(3)H]-Paroxetine binding was observed in 
      forebrain from E18. From birth (p0), binding was organized into neocortical 
      columns (75% higher at p10 than in adult) which declined toward adult levels 
      between p20 and p25. 4. MDMA treatment (20 mg x kg(-1) s.c. twice daily for four 
      days) commencing at developmental stages from E15 (treatment given to dams) to 
      p20, had no effect upon [(3)H]-paroxetine binding measured at p40. Treatments 
      started on p25 or later resulted in significant decreases in [(3)H]-paroxetine 
      binding (>or=46%). This was coincident with the development of adult patterns of 
      binding in forebrain. 5. Despite the lack of MDMA-induced neurotoxicity, rats 
      treated in utero (E15) showed increased lCMR(glu) in locus coeruleus (+37%), and 
      in areas receiving ascending noradrenergic innervation, such as anterior thalamus 
      (+44%) and septal nucleus (+24%). 6 These studies confirm that the susceptibility 
      of serotonergic terminals to the neurotoxic properties of MDMA is absent in the 
      immediate perinatal period, but also suggests that in utero MDMA exposure 
      produces significant long-term effects on cerebral function by a mechanism as yet 
      unknown.
FAU - Kelly, Paul A T
AU  - Kelly PA
AD  - Department of Clinical Neurosciences, University of Edinburgh, Western General 
      Hospital, Edinburgh, EH4 2XU, UK. pk@skull.dcn.ed.ac.uk
FAU - Ritchie, Isobel M
AU  - Ritchie IM
FAU - Quate, Linda
AU  - Quate L
FAU - McBean, Douglas E
AU  - McBean DE
FAU - Olverman, Henry J
AU  - Olverman HJ
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - 41VRH5220H (Paroxetine)
RN  - IY9XDZ35W2 (Glucose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/*pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Binding, Competitive
MH  - Brain/*drug effects/metabolism
MH  - Female
MH  - Glucose/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Paroxetine/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/pharmacokinetics
MH  - Time Factors
MH  - Tritium
PMC - PMC1573582
EDAT- 2002/11/14 04:00
MHDA- 2003/05/21 05:00
PMCR- 2003/12/01
CRDT- 2002/11/14 04:00
PHST- 2002/11/14 04:00 [pubmed]
PHST- 2003/05/21 05:00 [medline]
PHST- 2002/11/14 04:00 [entrez]
PHST- 2003/12/01 00:00 [pmc-release]
AID - 0704961 [pii]
AID - 10.1038/sj.bjp.0704961 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2002 Dec;137(7):963-70. doi: 10.1038/sj.bjp.0704961.