PMID- 20015297
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 159
IP  - 1
DP  - 2010 Jan
TI  - Dopamine transporter down-regulation following repeated cocaine: implications for 
      3,4-methylenedioxymethamphetamine-induced acute effects and long-term 
      neurotoxicity in mice.
PG  - 201-11
LID - 10.1111/j.1476-5381.2009.00522.x [doi]
AB  - BACKGROUND AND PURPOSE: 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine are 
      two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). 
      DAT availability regulates dopamine neurotransmission and uptake of MDMA-derived 
      neurotoxic metabolites. We aimed to determine the effect of cocaine pre-exposure 
      on the acute and long-term effects of MDMA in mice. EXPERIMENTAL APPROACH: Mice 
      received a course of cocaine (20 mg*kg(-1), x2 for 3 days) followed by MDMA (20 
      mg*kg(-1), x2, 3 h apart). Locomotor activity, extracellular dopamine levels and 
      dopaminergic neurotoxicity were determined. Furthermore, following the course of 
      cocaine, DAT density in striatal plasma membrane and endosome fractions was 
      measured. KEY RESULTS: Four days after the course of cocaine, challenge with MDMA 
      attenuated the MDMA-induced striatal dopaminergic neurotoxicity. 
      Co-administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented 
      cocaine protection. At the same time, after the course of cocaine, DAT density 
      was reduced in the plasma membrane and increased in the endosome fraction, and 
      this effect was prevented by NPC 15437. The course of cocaine potentiated the 
      MDMA-induced increase in extracellular dopamine and locomotor activity, following 
      challenge 4 days later, compared with those pretreated with saline. CONCLUSIONS 
      AND IMPLICATIONS: Repeated cocaine treatment followed by withdrawal protected 
      against MDMA-induced dopaminergic neurotoxicity by internalizing DAT via a 
      mechanism which may involve PKC. Furthermore, repeated cocaine followed by 
      withdrawal induced behavioural and neurochemical sensitization to MDMA, measures 
      which could be indicative of increased rewarding effects of MDMA.
FAU - Peraile, I
AU  - Peraile I
AD  - Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, 
      Madrid, Spain.
FAU - Torres, E
AU  - Torres E
FAU - Mayado, A
AU  - Mayado A
FAU - Izco, M
AU  - Izco M
FAU - Lopez-Jimenez, A
AU  - Lopez-Jimenez A
FAU - Lopez-Moreno, J A
AU  - Lopez-Moreno JA
FAU - Colado, M I
AU  - Colado MI
FAU - O'Shea, E
AU  - O'Shea E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091210
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 136449-85-9 (NPC 15437)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Membrane/drug effects/metabolism
MH  - Cocaine/administration & dosage/*pharmacology
MH  - Corpus Striatum/metabolism
MH  - Dopamine/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/*drug effects/metabolism
MH  - Down-Regulation/drug effects
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/etiology/*prevention & control
MH  - Piperidines/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Reward
MH  - Time Factors
PMC - PMC2823365
EDAT- 2009/12/18 06:00
MHDA- 2010/04/24 06:00
PMCR- 2011/01/01
CRDT- 2009/12/18 06:00
PHST- 2009/12/18 06:00 [entrez]
PHST- 2009/12/18 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - BPH522 [pii]
AID - 10.1111/j.1476-5381.2009.00522.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Jan;159(1):201-11. doi: 10.1111/j.1476-5381.2009.00522.x. 
      Epub 2009 Dec 10.