PMID- 28190519
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20180301
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 81
IP  - 11
DP  - 2017 Jun 1
TI  - Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in 
      Control of Alcohol-Seeking Behavior.
PG  - 907-917
LID - S0006-3223(17)30001-X [pii]
LID - 10.1016/j.biopsych.2016.12.026 [doi]
AB  - BACKGROUND: Dysfunction of the glutamatergic system has been implicated in 
      alcohol addiction; however, the molecular underpinnings of this phenomenon are 
      still poorly understood. In the current study we have investigated the possible 
      function of matrix metalloproteinase-9 (MMP-9) in alcohol addiction because this 
      protein has recently emerged as an important regulator of excitatory synaptic 
      plasticity. METHODS: For long-term studies of alcohol drinking in mice we used 
      IntelliCages. Dendritic spines were analyzed using Diolistic staining with DiI. 
      Whole-cell patch clamp was used to assess silent synapses. Motivation for alcohol 
      in human subjects was assessed on the basis of a Semi-Structured Assessment for 
      the Genetics of Alcoholism interview. RESULTS: Mice devoid of MMP-9 (MMP-9 
      knockout) drank as much alcohol as wild-type animals; however, they were impaired 
      in alcohol seeking during the motivation test and withdrawal. The deficit could 
      be rescued by overexpression of exogenous MMP-9 in the central nucleus of the 
      amygdala (CeA). Furthermore, the impaired alcohol seeking was associated with 
      structural alterations of dendritic spines in the CeA and, moreover, whole-cell 
      patch clamp analysis of the basal amygdala to CeA projections showed that alcohol 
      consumption and withdrawal were associated with generation of silent synapses. 
      These plastic changes were impaired in MMP-9 knockout mice. Finally, C/T 
      polymorphism of MMP-9 gene at position -1562, which upregulates MMP-9 expression, 
      correlated with increased motivation for alcohol in alcoholics. CONCLUSIONS: In 
      aggregate, our results indicate a novel mechanism of alcohol craving that 
      involves MMP-9-dependent synaptic plasticity in CeA.
CI  - Copyright (c) 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Stefaniuk, Marzena
AU  - Stefaniuk M
AD  - Laboratory of Neurobiology, the Nencki Institute, Warsaw.
FAU - Beroun, Anna
AU  - Beroun A
AD  - Laboratory of Neurobiology, the Nencki Institute, Warsaw.
FAU - Lebitko, Tomasz
AU  - Lebitko T
AD  - Laboratory of Neurobiology, the Nencki Institute, Warsaw.
FAU - Markina, Olga
AU  - Markina O
AD  - Laboratory of Neurobiology, the Nencki Institute, Warsaw.
FAU - Leski, Szymon
AU  - Leski S
AD  - Laboratory of Neuroinformatics, the Nencki Institute, Warsaw.
FAU - Meyza, Ksenia
AU  - Meyza K
AD  - Laboratory of Emotions Neurobiology, the Nencki Institute, Warsaw.
FAU - Grzywacz, Anna
AU  - Grzywacz A
AD  - Department of Psychiatry, Pomeranian Medical University, University of Szczecin, 
      Szczecin, Poland.
FAU - Samochowiec, Jerzy
AU  - Samochowiec J
AD  - Department of Psychiatry, Pomeranian Medical University, University of Szczecin, 
      Szczecin, Poland.
FAU - Samochowiec, Agnieszka
AU  - Samochowiec A
AD  - Department of Clinical Psychology, Institute of Psychology, University of 
      Szczecin, Szczecin, Poland.
FAU - Radwanska, Kasia
AU  - Radwanska K
AD  - Laboratory of Molecular Basis of Behavior, the Nencki Institute, Warsaw.
FAU - Kaczmarek, Leszek
AU  - Kaczmarek L
AD  - Laboratory of Neurobiology, the Nencki Institute, Warsaw. Electronic address: 
      l.kaczmarek@nencki.gov.pl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170105
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
CIN - Biol Psychiatry. 2017 Jun 1;81(11):900-902. PMID: 28502389
MH  - Adult
MH  - Alcohol Drinking/*physiopathology
MH  - Alcoholism/genetics
MH  - Amygdala/metabolism/pathology/*physiology
MH  - Animals
MH  - Dendritic Spines/pathology
MH  - Drug-Seeking Behavior/*physiology
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 9/biosynthesis/genetics/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Polymorphism, Single Nucleotide
MH  - Substance Withdrawal Syndrome/physiopathology
OTO - NOTNLM
OT  - Alcohol addiction
OT  - Central amygdala
OT  - MMP-9
OT  - Matrix metalloproteinase-9
OT  - Motivation
OT  - Silent synapses
EDAT- 2017/02/14 06:00
MHDA- 2018/02/27 06:00
CRDT- 2017/02/14 06:00
PHST- 2016/06/17 00:00 [received]
PHST- 2016/12/01 00:00 [revised]
PHST- 2016/12/16 00:00 [accepted]
PHST- 2017/02/14 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/02/14 06:00 [entrez]
AID - S0006-3223(17)30001-X [pii]
AID - 10.1016/j.biopsych.2016.12.026 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2017 Jun 1;81(11):907-917. doi: 10.1016/j.biopsych.2016.12.026. 
      Epub 2017 Jan 5.