PMID- 12105113
OWN - NLM
STAT- MEDLINE
DCOM- 20020802
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 965
DP  - 2002 Jun
TI  - Serotonergic neurotoxicity of MDMA (ecstasy) in the developing rat brain.
PG  - 373-80
AB  - The abused drug 3,4-methylenedioxymethamphetamine (MDMA) damages fine 
      serotonergic fibers and nerve terminals in adult organisms; however, developing 
      animals seem less susceptible to this effect. One proposed hypothesis is that 
      neonates are less sensitive to MDMA neurotoxicity because they fail to show 
      drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in 
      neonatal rats for 2 hours after each of twice-daily MDMA (10 mg/kg sc) or saline 
      injections given over the period from postnatal day (PD) 1 to 4. Other 
      drug-treated and control litters were maintained at normothermic temperatures 
      after injection. Differential core body temperatures were achieved by placing 
      pups (without the dam) in humidified, thermostatically controlled incubators. 
      Temperatures were monitored with a thermocouple probe at 30-minute intervals. 
      Pups subsequently remained undisturbed until sacrifice at PD 25 and PD 60 for 
      assessment of serotonergic damage by measuring 5-HT transporter (SERT) binding in 
      the hippocampus and neocortex as well as 5-HT and 5-HIAA concentrations (PD 25 
      only). Neonatal MDMA exposure led to significant reductions in both SERT binding 
      and 5-HT levels in the hippocampus at PD 25, independent of body temperature 
      during treatment. Hippocampal SERT binding increased between PD 25 and PD 60 in 
      both the MDMA and saline groups, but the MDMA-related deficit remained unchanged. 
      Interestingly, the neocortex showed no effect of MDMA at PD 25, but SERT binding 
      was significantly reduced at PD 60. Thus, MDMA can exert serotonergic 
      neurotoxicity in developing animals in the absence of elevated body temperature. 
      Hippocampal serotonergic innervation is damaged early, whereas neocortical 
      effects emerge at a later time. Furthermore, the tendency for serotonergic 
      recovery may be less after neonatal MDMA exposure than exposure of adult animals.
FAU - Meyer, Jerrold S
AU  - Meyer JS
AD  - Department of Psychology, Neuroscience and Behavior Program, University of 
      Massachusetts, Amherst, Massachusetts 01003, USA. jmeyer@psych.umass.edu
FAU - Ali, Syed F
AU  - Ali SF
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Neurotoxins)
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X77S6GMS36 (Homovanillic Acid)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Aging/physiology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brain/drug effects/*metabolism/pathology
MH  - Dopamine/metabolism
MH  - Female
MH  - Homovanillic Acid/metabolism
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - *Neurotoxins
MH  - Organ Specificity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/metabolism
EDAT- 2002/07/10 10:00
MHDA- 2002/08/03 10:01
CRDT- 2002/07/10 10:00
PHST- 2002/07/10 10:00 [pubmed]
PHST- 2002/08/03 10:01 [medline]
PHST- 2002/07/10 10:00 [entrez]
AID - 10.1111/j.1749-6632.2002.tb04179.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2002 Jun;965:373-80. doi: 10.1111/j.1749-6632.2002.tb04179.x.