PMID- 23466442
OWN - NLM
STAT- MEDLINE
DCOM- 20131218
LR  - 20161125
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 44
DP  - 2013 Jul 1
TI  - Heteromeric nicotinic receptors are involved in the sensitization and addictive 
      properties of MDMA in mice.
PG  - 201-9
LID - S0278-5846(13)00047-X [pii]
LID - 10.1016/j.pnpbp.2013.02.013 [doi]
AB  - We have investigated the effect of nicotinic receptor ligands in the behavioral 
      sensitization (hyperlocomotion) and rewarding properties (conditioned place 
      preference paradigm, CPP) of 3,4-methylenedioxy-methamphetamine (MDMA) in mice. 
      Each animal received intraperitoneal pretreatment with either saline, 
      dihydro-beta-erythroidine (DHbetaE, 1 mg/kg) or varenicline (VAR, 0.3 mg/kg), 15 min 
      prior to subcutaneous saline or MDMA (5 mg/kg), for 10 consecutive days. On day 
      1, both DHbetaE and VAR inhibited the MDMA-induced hyperlocomotion. After 10 days of 
      treatment, MDMA induced a hyperlocomotion that was not reduced (rather enhanced) 
      in antagonist-pretreated animals. This early hyperlocomotion was accompanied by a 
      significant increase in heteromeric nicotinic receptors in cortex that was not 
      blocked by DHbetaE or VAR. Behavioral sensitization to MDMA was highest 2 weeks 
      after the discontinuation of MDMA treatment. This additional increase in 
      sensitivity was prevented in animals pretreated with DHbetaE or VAR. At this time, 
      MDMA-treated mice showed a significant increase in heteromeric receptors in 
      cortex that was prevented by DHbetaE and VAR. An involvement of alpha7 nicotinic 
      receptors in this effect is ruled out. MDMA (10 mg/kg) induced positive CPP that 
      was abolished by DHbetaE (2 mg/kg) and VAR (2 mg/kg). Moreover, chronic nicotine 
      pretreatment (2 mg/kg, ip, b.i.d., for 14 days) caused MDMA, administered at a 
      low dose (3 mg/kg), to induce CPP, which would otherwise not occur. Finally, 
      present results point out that heteromeric nicotinic receptors are involved in 
      locomotor sensitization and addictive potential induced by MDMA. Thus, 
      varenicline might be a useful drug to treat both tobacco and MDMA abuse at once.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Ciudad-Roberts, Andres
AU  - Ciudad-Roberts A
AD  - Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), 
      Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain.
FAU - Camarasa, Jorge
AU  - Camarasa J
FAU - Pubill, David
AU  - Pubill D
FAU - Escubedo, Elena
AU  - Escubedo E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130304
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Benzazepines)
RN  - 0 (Cholinergic Agents)
RN  - 0 (Hallucinogens)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Nicotinic)
RN  - 10028-17-8 (Tritium)
RN  - 23255-54-1 (Dihydro-beta-Erythroidine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Benzazepines/pharmacology
MH  - Brain/diagnostic imaging/drug effects
MH  - Cholinergic Agents/pharmacokinetics
MH  - Conditioning, Operant/*drug effects
MH  - Dihydro-beta-Erythroidine/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Hallucinogens/*toxicity
MH  - Hyperkinesis/*chemically induced/metabolism
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Protein Binding/drug effects
MH  - Quinoxalines/pharmacology
MH  - Radionuclide Imaging
MH  - Receptors, Nicotinic/*metabolism
MH  - Substance-Related Disorders/etiology/*metabolism/physiopathology
MH  - Tritium/pharmacokinetics
MH  - Varenicline
EDAT- 2013/03/08 06:00
MHDA- 2013/12/19 06:00
CRDT- 2013/03/08 06:00
PHST- 2012/10/02 00:00 [received]
PHST- 2013/01/30 00:00 [revised]
PHST- 2013/02/21 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/12/19 06:00 [medline]
AID - S0278-5846(13)00047-X [pii]
AID - 10.1016/j.pnpbp.2013.02.013 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:201-9. doi: 
      10.1016/j.pnpbp.2013.02.013. Epub 2013 Mar 4.