title: Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  In aggregate, our results indicate a novel mechanism of alcohol craving that involves MMP-9-dependent synaptic plasticity in CeA.
authors.affiliation: Laboratory of Neurobiology, the Nencki Institute, Warsaw.
authors.forename: Marzena
authors.initials: M
authors.lastname: Stefaniuk
authors.affiliation: Laboratory of Neurobiology, the Nencki Institute, Warsaw.
authors.forename: Anna
authors.initials: A
authors.lastname: Beroun
authors.affiliation: Laboratory of Neurobiology, the Nencki Institute, Warsaw.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lebitko
authors.affiliation: Laboratory of Neurobiology, the Nencki Institute, Warsaw.
authors.forename: Olga
authors.initials: O
authors.lastname: Markina
authors.affiliation: Laboratory of Neuroinformatics, the Nencki Institute, Warsaw.
authors.forename: Szymon
authors.initials: S
authors.lastname: Leski
authors.affiliation: Laboratory of Emotions Neurobiology, the Nencki Institute, Warsaw.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Meyza
authors.affiliation: Department of Psychiatry, Pomeranian Medical University, University of Szczecin, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Grzywacz
authors.affiliation: Department of Psychiatry, Pomeranian Medical University, University of Szczecin, Szczecin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Samochowiec
authors.affiliation: Department of Clinical Psychology, Institute of Psychology, University of Szczecin, Szczecin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Samochowiec
authors.affiliation: Laboratory of Molecular Basis of Behavior, the Nencki Institute, Warsaw.
authors.forename: Kasia
authors.initials: K
authors.lastname: Radwanska
authors.affiliation: Laboratory of Neurobiology, the Nencki Institute, Warsaw. Electronic address: l.kaczmarek@nencki.gov.pl.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000235:genetics; D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000818:Animals; D049229:Dendritic Spines / Q000473:pathology; D058999:Drug-Seeking Behavior / Q000502:physiology*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D020780:Matrix Metalloproteinase 9
keywords: Alcohol addiction; Central amygdala; MMP-9; Matrix metalloproteinase-9; Motivation; Silent synapses