Dataset Information
Heroin Seeking and Extinction From Seeking Activate Matrix Metalloproteinases at Synapses on Distinct Subpopulations of Accumbens Cells.
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ABSTRACT: Background
Seeking addictive drugs is regulated by synaptic plasticity in the nucleus accumbens core and involves distinct plasticity in D1 and D2 receptor-expressing medium spiny neurons (D1/2-MSNs). However, it is unknown how differential plasticity between the two cell types is coordinated. Synaptic plasticity and seeking behavior induced by drug-paired cues depends not only on plasticity in the canonical pre- and postsynapse, but also on cue-induced changes in astrocytes and the extracellular matrix adjacent to the synapse. Drug cue-induced signaling in the extracellular matrix is regulated by catalytic activity of matrix metalloproteinases MMP-2,9. We hypothesized that the cell type-specific synaptic plasticity is associated with parallel cell-specific activity of MMP-2 and MMP-9.Methods
Transgenic rats were trained on a heroin self-administration protocol in which a light/tone cue was paired with heroin delivery, followed by 2 weeks of drug withdrawal, and then reinstated to heroin-conditioned cues. Confocal microscopy was used to make morphological measurements in membrane reporter-transduced D1- and D2-MSNs and astrocytes, and MMP-2,9 gelatinase activity adjacent to cell surfaces was quantified using in vivo zymography.Results
Presenting heroin-paired cues transiently increased MMP-9 activity around D1-MSN dendritic spines and synapse-proximal astroglial processes. Conversely, extinction training induced long-lasting increases in MMP-2 activity adjacent to D2-MSN synapses. Moreover, heroin-paired cues increased tissue inhibitor of metalloproteinases TIMP-1,2, which caused transient inhibition of MMP-2 activity around D2-MSNs during cue-induced heroin seeking.Conclusions
The differential regulation of heroin seeking and extinguished seeking by different MMP subtypes on distinct cell populations poses MMP-2,9 activity as an important mediator and contributor in heroin-induced cell-specific synaptic plasticity.
SUBMITTER: Chioma VC
PROVIDER: S-EPMC8434769 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Heroin Seeking and Extinction From Seeking Activate Matrix Metalloproteinases at Synapses on Distinct Subpopulations of Accumbens Cells.
Biological psychiatry 20201209 10
<h4>Background</h4>Seeking addictive drugs is regulated by synaptic plasticity in the nucleus accumbens core and involves distinct plasticity in D<sub>1</sub> and D<sub>2</sub> receptor-expressing medium spiny neurons (D1/2-MSNs). However, it is unknown how differential plasticity between the two cell types is coordinated. Synaptic plasticity and seeking behavior induced by drug-paired cues depends not only on plasticity in the canonical pre- and postsynapse, but also on cue-induced changes in a ...[more]
