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Matrix metalloproteinase activity during methamphetamine cued relapse.

Stacia I Lewandowski1, Ritchy Hodebourg1, Samuel K Wood1

  • 1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.

Addiction Biology
|May 15, 2023
PubMed
Summary
This summary is machine-generated.

Matrix metalloproteinase (MMP) activation in the nucleus accumbens core increases during cue-induced methamphetamine seeking. However, this MMP activity does not correlate with the escalation of seeking behavior during extended abstinence.

Keywords:
abstinenceadditionmatrix metalloproteinasesmethamphetaminerelapse

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Area of Science:

  • Neuroscience
  • Addiction Research
  • Molecular Biology

Background:

  • Relapse to drug seeking is linked to synaptic remodeling triggered by drug-associated cues.
  • Matrix metalloproteinases (MMPs) play a role in extracellular matrix signaling during this remodeling process.

Purpose of the Study:

  • To investigate if matrix metalloproteinase (MMP) activity increases in the nucleus accumbens core (NAcore) during cue-induced methamphetamine seeking in a rat model.
  • To determine if MMP activity correlates with the escalation of methamphetamine seeking behavior over time.

Main Methods:

  • Rats underwent methamphetamine or saline self-administration, followed by abstinence periods of 7 or 30 days.
  • Gelatinase activity (MMP-2,9) in the NAcore was quantified using a fluorescent substrate during cue-induced relapse testing.

Main Results:

  • MMP-2,9 activity was elevated in the NAcore upon presentation of methamphetamine cues after both 7 and 30 days of abstinence.
  • Despite an increase in cue-induced seeking behavior between 7 and 30 days of abstinence, MMP-2,9 activity did not further increase.

Conclusions:

  • MMP activation is involved in the neural response to methamphetamine cues during relapse.
  • MMP activation during cue-induced seeking does not parallel the increase in seeking behavior observed with extended drug abstinence.