Mephedrone Impact on Matrix Metalloproteinases Activity - Do they Influence the Memory Processes?

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Author(s): Anna Boguszewska-Czubara*, Jacek Kurzepa, Grażyna Biała, Katarzyna Kaszubska, Karolina Grot, Piotr Tarkowski, Joanna Kowalczyk, Serena Silvestro, Caterina Faggio, Barbara Budzyńska.

Journal Name: Current Molecular Pharmacology

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Background: The use of drugs of addiction, as mephedrone, is associated with functional neuronal disorders due to remodeling of the nervous tissue. Key enzymes in remodeling are extracellular matrix (ECM) proteases like matrix metalloproteases (MMPs). Recently, MMPs have been of great interest as some studies point to a fact that the alterations in structural remodeling of synaptic connections modify learning-dependent changes, which remain active even after a prolonged period of abstinence. This entails a continuous development of dependence.

Objectives: The aim of the study was to determine the influence of subchronic exposure to three different doses of mephedrone on the activity of MMP-2 and 9 in hippocampus and prefrontal cortex and how this was correlated with memory processes in mice.

Methods: The homogenates of hippocampus and cortex were assayed for MMP-2 and MMP-9 activity by gelatin zymography. Memory consolidation processes were evaluated in the passive avoidance (PA) test.

Results: The study confirmed the dose-dependent increase in activity of MMP-2 and -9 exerted by subchronic administration of mephedrone. Moreover, the highest does of mephedrone attenuated consolidation of memory and learning processes.

Conclusions: We could hypothesize that inhibition of MMPs can be considered as a therapeutic option for the treatment of addictive behaviors associated with cognitive processes. Moreover, further studies are required to find out if elevated activities of MMPs contribute to brain damage or recovery from brain damage caused directly by mephedrone.

Keywords: mephedrone, mice, matrix metalloproteinases, memory, hippocampus, prefrontal cortex, cognitive processes

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1874467212666190114154307
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