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Activation of mu opioid receptors in the striatum differentially augments methamphetamine-induced gene expression and

Kristen A Horner1, John C Hebbard, Anna S Logan

  • 1Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA. horner_ka@mercer.edu

Journal of Neurochemistry
|December 14, 2011
PubMed

Insights

Mu opioid receptor activation enhances methamphetamine-induced stereotypy and zif/268 gene expression in the striatum. However, it differentially affects other gene responses, suggesting prodynorphin may mitigate overstimulation.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Mu opioid receptors are concentrated in the striatal patch compartment.
  • These receptors are implicated in methamphetamine's effects on gene expression and behavior.

Purpose of the Study:

  • To investigate how mu opioid receptor activation influences methamphetamine-induced stereotypy.
  • To examine the impact on gene expression (prodynorphin, c-fos, arc, zif/268) in striatal compartments.
  • To understand the relationship between gene expression and stereotypy.

Main Methods:

  • Rats received intrastriatal infusions of DAMGO (mu opioid receptor agonist).
  • Animals were treated with methamphetamine and tissue collected at different time points.
  • Gene expression levels and stereotypy were quantified in striatal patch and matrix.

Main Results:

  • DAMGO amplified methamphetamine-induced zif/268 mRNA in both patch and matrix.
  • Prodynorphin expression increased in the dorsolateral patch compartment.
  • DAMGO enhanced methamphetamine stereotypy, with a negative correlation between prodynorphin levels and stereotypy.

Conclusions:

  • Mu opioid receptors contribute to methamphetamine-induced stereotypy.
  • These receptors differentially modulate methamphetamine's genomic effects.
  • Prodynorphin may act as a counterbalance to striatal overstimulation by methamphetamine.

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