PMID- 16901518
OWN - NLM
STAT- MEDLINE
DCOM- 20061106
LR  - 20131121
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 51
IP  - 4
DP  - 2006 Sep
TI  - Protection against MDMA-induced dopaminergic neurotoxicity in mice by 
      methyllycaconitine: involvement of nicotinic receptors.
PG  - 885-95
AB  - Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic 
      neurotoxin in mice. Previous studies demonstrated the participation of alpha-7 
      nicotinic receptors (nAChR) in the neurotoxic effect of methamphetamine. The aim 
      of this paper was to study the role of this receptor type in the acute effects 
      and neurotoxicity of MDMA in mice. In vivo, methyllycaconitine (MLA), a specific 
      alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at 
      dopaminergic but not at serotonergic level, without affecting MDMA-induced 
      hyperthermia. Glial activation was also fully prevented by MLA. In vitro, MDMA 
      induced intrasynaptosomal reactive oxygen species (ROS) generation, which was 
      calcium-, nitric-oxide synthase-, and protein kinase C-dependent. Also, the 
      increase in ROS was prevented by MLA and alpha-bungarotoxin. Experiments with 
      reserpine point to endogenous dopamine (DA) as the main source of MDMA-induced 
      ROS. MLA also brought the MDMA-induced inhibition of [3H]DA uptake down, from 73% 
      to 11%. We demonstrate that a coordinated activation of alpha-7 nAChR, blockade 
      of DA transporter function and displacement of DA from intracellular stores 
      induced by MDMA produces a neurotoxic effect that can be prevented by MLA, 
      suggesting that alpha-7 nAChR have a key role in the MDMA neurotoxicity in mice; 
      however, the involvement of nicotinic receptors containing the beta2 subunit 
      cannot be conclusively ruled out.
FAU - Chipana, C
AU  - Chipana C
AD  - Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Universitat de 
      Barcelona, Av. Joan XXIII s/n., Zona Universitaria Pedralbes, 08028 Barcelona, 
      Spain.
FAU - Camarasa, J
AU  - Camarasa J
FAU - Pubill, D
AU  - Pubill D
FAU - Escubedo, E
AU  - Escubedo E
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060808
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Nicotinic Antagonists)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Nicotinic)
RN  - 10028-17-8 (Tritium)
RN  - 21019-30-7 (methyllycaconitine)
RN  - 50370-56-4 ((1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- 
      azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
RN  - X8YN71D5WC (Aconitine)
SB  - IM
MH  - Aconitine/*analogs & derivatives/therapeutic use
MH  - Analysis of Variance
MH  - Animals
MH  - Cocaine/analogs & derivatives/pharmacokinetics
MH  - Disease Models, Animal
MH  - Dopamine/*metabolism
MH  - Dopamine Uptake Inhibitors/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Flow Cytometry/methods
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Neuroprotective Agents/*therapeutic use
MH  - Neurotoxicity Syndromes/*drug therapy/etiology
MH  - Nicotinic Agonists/pharmacology
MH  - Nicotinic Antagonists/pharmacology
MH  - Radioligand Assay/methods
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Nicotinic/*physiology
MH  - Synaptosomes/drug effects/metabolism
MH  - Tritium/metabolism
EDAT- 2006/08/12 09:00
MHDA- 2006/11/07 09:00
CRDT- 2006/08/12 09:00
PHST- 2006/03/28 00:00 [received]
PHST- 2006/05/30 00:00 [revised]
PHST- 2006/05/30 00:00 [accepted]
PHST- 2006/08/12 09:00 [pubmed]
PHST- 2006/11/07 09:00 [medline]
PHST- 2006/08/12 09:00 [entrez]
AID - S0028-3908(06)00169-9 [pii]
AID - 10.1016/j.neuropharm.2006.05.032 [doi]
PST - ppublish
SO  - Neuropharmacology. 2006 Sep;51(4):885-95. doi: 10.1016/j.neuropharm.2006.05.032. 
      Epub 2006 Aug 8.