Drug addiction has been characterized as a disorder of maladaptive synaptic plasticity.
Irrespective of the mechanism of action of the drug being abused, they all produce
similar behavioral endpoints: craving and vulnerability to relapse during periods
of abstinence, loss of control over intake, and continued use despite negative consequences.
As such, identifying shared neurobiological features across different classes of drugs
may identify points of attack that can be used to develop efficacious therapeutics
for the treatment of addiction. One such shared neurobiological trait is aberrant
extracellular matrix remodeling, in particular by matrix metalloproteinase-9 (MMP-9).
MMPs are Zn2+-dependent proteolytic enzymes that are primary regulators of the composition and
integrity of the extracellular matrix. Dysregulation of MMP-9 activity has been reported
following chronic use of alcohol, nicotine, opiates, cocaine, and methamphetamine
(
1
). A family of 23 extracellular matrix–remodeling MMPs were originally described for
their roles in angiogenesis, tumor cell invasion, and wound healing, and were thought
to function primarily in regulating structural support surrounding cells (
2
). In the brain, however, they have more recently gained recognition for being important
signaling molecules that regulate both structural and functional plasticity, primarily
at excitatory synapses (
1
).To read this article in full you will need to make a payment
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References
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Article info
Publication history
Accepted:
February 28,
2017
Received:
February 28,
2017
Identification
Copyright
© Society of Biological Psychiatry, 2017.
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- Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking BehaviorBiological PsychiatryVol. 81Issue 11
- PreviewDysfunction 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.
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