PMID- 12379247
OWN - NLM
STAT- MEDLINE
DCOM- 20030110
LR  - 20190712
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 114
IP  - 4
DP  - 2002
TI  - Unilateral infusion of a dopamine transporter antisense into the substantia nigra 
      protects against MDMA-induced serotonergic deficits in the ipsilateral striatum.
PG  - 917-24
AB  - The present study was designed to elucidate the consequences of antisense 
      oligonucleotide-mediated knockdown of striatal dopamine reuptake transporters on 
      3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity. Antisense 
      oligonucleotide complementary to the mRNA translational start site of the rat 
      dopamine transporter was delivered by constant (7 days) intranigral infusion with 
      an osmotic minipump. Delivery of the antisense oligonucleotide by this method 
      resulted in a 70% reduction in the density of the dopamine transporter in the 
      ipsilateral striatum, as measured by [(3)H]mazindol binding. The effect of this 
      transporter knockdown on MDMA-induced serotonergic neurotoxicity was then 
      examined. MDMA (2x20 mg/kg, s.c., given 12 h apart) administered to control rats 
      produced hyperthermia following the first dose and led to a 45-50% reduction in 
      striatal serotonin, 5-hydroxyindoleacetic acid, and serotonin reuptake 
      transporter density 1 week after the second dose. Conversely, in antisense-, but 
      not missense-treated rats, a significant attenuation of MDMA-induced 
      neurotoxicity was observed only in the ipsilateral striatum. The hyperthermic 
      response elicited by MDMA was not altered by prior administration of antisense. 
      In vivo microdialysis revealed that the antisense treatment attenuated 
      MDMA-induced dopamine release in the ipsilateral striatum. These results suggest 
      that the dopamine transporter plays an essential role in the neurodegeneration 
      induced by MDMA, and provides additional support for the hypothesis that 
      extracellular dopamine is involved in the neurotoxic process, at least in the 
      striatum.
FAU - Kanthasamy, A
AU  - Kanthasamy A
AD  - Department of Biomedical Sciences, School of Veterinary Medicine, Iowa State 
      University, Ames 50011, USA.
FAU - Sprague, J E
AU  - Sprague JE
FAU - Shotwell, J R
AU  - Shotwell JR
FAU - Nichols, D E
AU  - Nichols DE
LA  - eng
GR  - DA04758/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 10028-17-8 (Tritium)
RN  - 333DO1RDJY (Serotonin)
RN  - C56709M5NH (Mazindol)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Corpus Striatum/*metabolism
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Dopamine Uptake Inhibitors/metabolism/pharmacology
MH  - Fever/chemically induced
MH  - Male
MH  - Mazindol/metabolism/pharmacology
MH  - Membrane Glycoproteins/metabolism
MH  - Membrane Transport Proteins/*genetics/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - *Nerve Tissue Proteins
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*toxicity
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Substantia Nigra/*physiology
MH  - Tritium
EDAT- 2002/10/16 04:00
MHDA- 2003/01/11 04:00
CRDT- 2002/10/16 04:00
PHST- 2002/10/16 04:00 [pubmed]
PHST- 2003/01/11 04:00 [medline]
PHST- 2002/10/16 04:00 [entrez]
AID - S0306452202003688 [pii]
AID - 10.1016/s0306-4522(02)00368-8 [doi]
PST - ppublish
SO  - Neuroscience. 2002;114(4):917-24. doi: 10.1016/s0306-4522(02)00368-8.