PMID- 14735293
OWN - NLM
STAT- MEDLINE
DCOM- 20041122
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 173
IP  - 3-4
DP  - 2004 May
TI  - Effect of 5-HT depletion by MDMA on hyperthermia and Arc mRNA induction in rat 
      brain.
PG  - 346-52
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) administration to rats 
      produces an acute hyperthermic response and induces localised neuronal 
      activation, which can be visualised via expression of immediate-early genes. The 
      pharmacological and anatomical basis of these effects are unclear. At high doses, 
      MDMA also causes selective neurotoxicity at serotonergic nerve terminals. 
      OBJECTIVE: We investigated the effect of 5-hydroxytryptamine (5-HT) depletion on 
      the acute hyperthermic response to MDMA and the pattern of neuronal excitation 
      indicated by Arc (activity-regulated cytoskeleton associated gene) in naive rats 
      and following administration of MDMA at a neurotoxic dose. METHODS: Expression of 
      Arc mRNA was investigated by in situ hybridisation histochemistry using 
      35S-labelled oligonucleotide probe. RESULTS: MDMA induced a significant 
      hyperthermia together with increased Arc mRNA expression in cortical regions, 
      caudate-putamen and CA1 hippocampus but not hypothalamus. At 21 days after a 
      neurotoxic dose of MDMA, brain 5-HT and 5-HIAA levels were significantly reduced 
      by 21-32%. In these animals, both the hyperthermic response and the pattern and 
      extent of Arc mRNA expression induced by a subsequent dose of MDMA were 
      unaltered. However, basal Arc expression was significantly increased in cortical 
      regions and CA1 hippocampus. CONCLUSION: We conclude that the acute hyperthermic 
      response induced by MDMA is not attenuated by moderate depletion of 5-HT, further 
      questioning mediation via a serotonergic mechanism. Arc mRNA induction by MDMA 
      exhibits highly localised expression, which is not altered following 5-HT 
      depletion. However, following a neurotoxic dose of MDMA, basal expression of Arc 
      is increased, particularly in cortex and CA1, suggesting that mechanisms 
      underlying synaptic plasticity might also be modified.
FAU - Beveridge, Thomas J R
AU  - Beveridge TJ
AD  - School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK.
FAU - Mechan, Annis O
AU  - Mechan AO
FAU - Sprakes, Marie
AU  - Sprakes M
FAU - Pei, Qi
AU  - Pei Q
FAU - Zetterstrom, Tyra S C
AU  - Zetterstrom TS
FAU - Green, A Richard
AU  - Green AR
FAU - Elliott, J Martin
AU  - Elliott JM
LA  - eng
PT  - Journal Article
DEP - 20040120
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - 333DO1RDJY (Serotonin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Cytoskeletal Proteins
MH  - Fever/chemically induced/*metabolism
MH  - Immediate-Early Proteins/*biosynthesis/genetics
MH  - In Situ Hybridization
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Nerve Tissue Proteins/*biosynthesis/genetics
MH  - RNA, Messenger/*biosynthesis
MH  - Rats
MH  - Serotonin/*metabolism
MH  - Serotonin Antagonists/administration & dosage/*toxicity
EDAT- 2004/01/22 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/01/22 05:00
PHST- 2003/08/02 00:00 [received]
PHST- 2003/11/27 00:00 [accepted]
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - 10.1007/s00213-003-1753-y [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2004 May;173(3-4):346-52. doi: 
      10.1007/s00213-003-1753-y. Epub 2004 Jan 20.