PMID- 18662325
OWN - NLM
STAT- MEDLINE
DCOM- 20081107
LR  - 20131121
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 106
IP  - 6
DP  - 2008 Sep
TI  - Augmentation of serotonin release by sustained exposure to MDMA and 
      methamphetamine in rat organotypic mesencephalic slice cultures containing raphe 
      serotonergic neurons.
PG  - 2410-20
LID - 10.1111/j.1471-4159.2008.05583.x [doi]
AB  - Several lines of evidence suggest the involvement of the raphe-serotonergic 
      neurons in addiction to psychostimulants and some recreational drugs. In this 
      study, we established rat organotypic mesencephalic slice cultures containing the 
      raphe nuclei and examined the effects of sustained exposure to 
      3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH). 
      Immunostaining for tryptophan hydroxylase (TPH) studies revealed that 
      serotonergic neurons were abundant in the slice cultures. Sustained exposure to 
      MDMA and METH (1-1000 microM) for 4 days had little effect on the serotonin 
      tissue content, [(3)H]citalopram binding, or expression/phosphorylation of TPH. 
      Treatment with MDMA or METH for 30 min increased serotonin release in a 
      concentration-dependent manner. Slice cultures were exposed to MDMA for 4 days 
      following a 1-day withdrawal period and then challenged with MDMA (10 microM). 
      Sustained MDMA exposure augmented MDMA-induced serotonin release in a 
      concentration-dependent manner, indicating serotonergic sensitization. Similar 
      serotonergic sensitization was observed for METH. The development of MDMA-induced 
      serotonergic sensitization was attenuated by the NMDA receptor antagonist, MK-801 
      (10 microM). These results suggest that in mesencephalic slice cultures sustained 
      MDMA or METH exposure induces serotonergic sensitization through activation of 
      NMDA receptors without serotonergic neurotoxicity. The in vitro model system 
      could help to elucidate the mechanisms underlying drug addiction.
FAU - Higuchi, Megumi
AU  - Higuchi M
AD  - Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, 
      Kyoto University, Kyoto, Japan.
FAU - Suzuki, Yuichi
AU  - Suzuki Y
FAU - Yatani, Yumi
AU  - Yatani Y
FAU - Kitagawa, Yutaka
AU  - Kitagawa Y
FAU - Nagayasu, Kazuki
AU  - Nagayasu K
FAU - Shirakawa, Hisashi
AU  - Shirakawa H
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
FAU - Kaneko, Shuji
AU  - Kaneko S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080724
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Amphetamine-Related Disorders/metabolism/physiopathology
MH  - Animals
MH  - Animals, Newborn
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance/drug effects/physiology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Mesencephalon/*drug effects/metabolism
MH  - Methamphetamine/*pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Organ Culture Techniques
MH  - Raphe Nuclei/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/metabolism
MH  - Serotonin/*metabolism
MH  - Synaptic Transmission/drug effects/physiology
MH  - Up-Regulation/drug effects/physiology
EDAT- 2008/07/30 09:00
MHDA- 2008/11/08 09:00
CRDT- 2008/07/30 09:00
PHST- 2008/07/30 09:00 [pubmed]
PHST- 2008/11/08 09:00 [medline]
PHST- 2008/07/30 09:00 [entrez]
AID - JNC5583 [pii]
AID - 10.1111/j.1471-4159.2008.05583.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Sep;106(6):2410-20. doi: 10.1111/j.1471-4159.2008.05583.x. Epub 
      2008 Jul 24.