PMID- 23261423
OWN - NLM
STAT- MEDLINE
DCOM- 20130910
LR  - 20161125
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 35
DP  - 2013 Mar
TI  - 3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of 
      central nicotinic receptors in rats and potentiates the regulatory effects of 
      nicotine on these receptors.
PG  - 41-9
LID - S0161-813X(12)00299-9 [pii]
LID - 10.1016/j.neuro.2012.11.008 [doi]
AB  - Nicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its 
      effects through activation of central nicotinic acetylcholine receptors (nAChR), 
      which become up-regulated after chronic administration. Recent work has 
      demonstrated that the recreational drug 3,4-methylenedioxy-methamphetamine (MDMA) 
      has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells. 
      Tobacco and MDMA are often consumed together. In the present work we studied the 
      in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or 
      combined with a chronic schedule of NIC, on the density of nAChR and on serotonin 
      reuptake transporters. MDMA induced significant decreases in [(3)H]paroxetine 
      binding in the cortex and hippocampus measured 24h after the last dose and these 
      decreases were not modified by the association with NIC. In the prefrontal 
      cortex, NIC and MDMA each induced significant increases in [(3)H]epibatidine 
      binding (29.5 and 34.6%, respectively) with respect to saline-treated rats, and 
      these increases were significantly potentiated (up to 72.1%) when the two drugs 
      were associated. Also in this area, [(3)H]methyllycaconitine binding was 
      increased a 42.1% with NIC+MDMA but not when they were given alone. In the 
      hippocampus, MDMA potentiated the alpha7 regulatory effects of NIC (raising a 25.5% 
      increase to 52.5%) but alone was devoid of effect. MDMA had no effect on 
      heteromeric nAChR in striatum and a coronal section of the midbrain containing 
      superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental 
      area. Specific immunoprecipitation of solubilised receptors suggests that the 
      up-regulated heteromeric nAChRs contain alpha4 and beta2 subunits. Western blots with 
      specific alpha4 and alpha7 antibodies showed no significant differences between the 
      groups, indicating that, as reported for nicotine, up-regulation caused by MDMA 
      is due to post-translational events rather than increased receptor synthesis.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Pubill, David
AU  - Pubill D
AD  - Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Nucli Universitari 
      de Pedralbes, Universitat de Barcelona, Institut de Biomedicina de la UB (IBUB), 
      08028 Barcelona, Spain. d.pubill@ub.edu
FAU - Garcia-Rates, Sara
AU  - Garcia-Rates S
FAU - Camarasa, Jordi
AU  - Camarasa J
FAU - Escubedo, Elena
AU  - Escubedo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121219
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, rat)
RN  - 21019-30-7 (methyllycaconitine)
RN  - 41VRH5220H (Paroxetine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - M6K314F1XX (epibatidine)
RN  - X8YN71D5WC (Aconitine)
SB  - IM
MH  - Aconitine/analogs & derivatives/metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Brain/*drug effects/metabolism
MH  - Bridged Bicyclo Compounds, Heterocyclic/metabolism
MH  - Drug Administration Schedule
MH  - Drug Synergism
MH  - Immunoprecipitation
MH  - Injections, Subcutaneous
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*pharmacology
MH  - Nicotine/administration & dosage/*pharmacology
MH  - Nicotinic Agonists/administration & dosage/*pharmacology
MH  - Paroxetine/metabolism
MH  - Pyridines/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nicotinic/*drug effects/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/drug effects/metabolism
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2012/12/25 06:00
MHDA- 2013/09/11 06:00
CRDT- 2012/12/25 06:00
PHST- 2012/09/20 00:00 [received]
PHST- 2012/11/19 00:00 [revised]
PHST- 2012/11/22 00:00 [accepted]
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/09/11 06:00 [medline]
AID - S0161-813X(12)00299-9 [pii]
AID - 10.1016/j.neuro.2012.11.008 [doi]
PST - ppublish
SO  - Neurotoxicology. 2013 Mar;35:41-9. doi: 10.1016/j.neuro.2012.11.008. Epub 2012 
      Dec 19.