PMID- 21896278
OWN - NLM
STAT- MEDLINE
DCOM- 20120801
LR  - 20211020
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 61
IP  - 8
DP  - 2011 Dec
TI  - Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine 
      (MPEP) microinfusions into the nucleus accumbens shell or ventral tegmental area 
      attenuate the reinforcing effects of nicotine in rats.
PG  - 1399-405
LID - 10.1016/j.neuropharm.2011.08.028 [doi]
AB  - Systemic administration of the mGlu5 receptor antagonist 
      2-methyl-6-(phenylethynyl)-pyridine (MPEP) was previously shown to selectively 
      attenuate nicotine self-administration without affecting food-maintained 
      responding in rats. Glutamatergic neurotransmission in the ventral tegmental area 
      (VTA) and nucleus accumbens (NAcc) shell plays an important role in the 
      reinforcing effects of nicotine. To determine the brain sites that may mediate 
      the systemic effects of MPEP on nicotine self-administration, the present study 
      investigated the effects of MPEP microinfusions into the VTA or the NAcc shell on 
      nicotine and food self-administration in separate groups of rats. Administration 
      of low MPEP doses (0, 0.5, 1, and 2 mug/0.5 mul/side) microinfused into the NAcc 
      shell had no effect on nicotine self-administration, whereas higher MPEP doses 
      (0, 10, 20, and 40 mug/0.5 mul/side) microinfused into the NAcc shell 
      dose-dependently attenuated nicotine self-administration without affecting 
      food-maintained responding. Microinfusions of MPEP into the VTA (0, 10, 20, and 
      40 mug/0.5 mul/side) significantly decreased both nicotine and food 
      self-administration at 20 mug/0.5 mul/side but did not affect responding for either 
      reinforcer at 40mug/0.5 mul/side. This lack of effect of 40 mug/0.5 mul/side MPEP on 
      either nicotine or food self-administration when administered into the VTA may be 
      attributable either to actions of MPEP at presynaptic mGlu5 receptors or at 
      targets other than mGlu5 receptors. Importantly, anatomical control injections 
      2mm above the NAcc shell or the VTA using the most effective MPEP dose in the two 
      regions did not result in attenuation of nicotine self-administration. In 
      conclusion, MPEP microinfusions in the VTA or NAcc shell attenuates the 
      reinforcing effects of nicotine possibly via blockade of mGlu5 receptors located 
      in these regions.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - D'Souza, Manoranjan S
AU  - D'Souza MS
AD  - Department of Psychiatry, School of Medicine, University of California, San 
      Diego, La Jolla, CA 92093, USA.
FAU - Markou, Athina
AU  - Markou A
LA  - eng
GR  - R01 DA011946/DA/NIDA NIH HHS/United States
GR  - R01 DA011946-11/DA/NIDA NIH HHS/United States
GR  - R56 DA011946/DA/NIDA NIH HHS/United States
GR  - 1R01DA11946/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110831
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Pyridines)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 7VC0YVI27Y (6-methyl-2-(phenylethynyl)pyridine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Conditioning, Operant/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Food Preferences/drug effects
MH  - Male
MH  - Nicotine/*administration & dosage
MH  - Nicotinic Agonists/*administration & dosage
MH  - Nucleus Accumbens/*drug effects/physiology
MH  - Pyridines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Reinforcement Schedule
MH  - *Reinforcement, Psychology
MH  - Self Administration
MH  - Ventral Tegmental Area/*drug effects/physiology
PMC - PMC3189265
MID - NIHMS323670
EDAT- 2011/09/08 06:00
MHDA- 2012/08/02 06:00
PMCR- 2012/12/01
CRDT- 2011/09/08 06:00
PHST- 2010/12/16 00:00 [received]
PHST- 2011/08/03 00:00 [revised]
PHST- 2011/08/19 00:00 [accepted]
PHST- 2011/09/08 06:00 [entrez]
PHST- 2011/09/08 06:00 [pubmed]
PHST- 2012/08/02 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S0028-3908(11)00361-3 [pii]
AID - 10.1016/j.neuropharm.2011.08.028 [doi]
PST - ppublish
SO  - Neuropharmacology. 2011 Dec;61(8):1399-405. doi: 
      10.1016/j.neuropharm.2011.08.028. Epub 2011 Aug 31.