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[D-Ala2, D-Leu5]enkephalin blocks the methamphetamine-induced c-fos mRNA increase in mouse striatum

T Hayashi1, L I Tsao, J L Cadet

  • 1Molecular Neuropsychiatry Section, Intramural Research Program, National Institute on Drug Abuse/NIH, Baltimore, MD 21224, USA.

European Journal of Pharmacology
|March 19, 1999
PubMed

Insights

Methamphetamine increases c-fos mRNA in mouse striatum. Delta-opioid receptor agonists like DADLE reduce this effect, suggesting endogenous opioids may counteract psychostimulant actions.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Methamphetamine is a psychostimulant drug with known effects on gene expression.
  • The striatum is a key brain region involved in reward and motor control, affected by psychostimulants.
  • Opioid receptors, particularly delta-opioid receptors, play roles in modulating neuronal activity.

Purpose of the Study:

  • To investigate the effect of methamphetamine on c-fos mRNA expression in the mouse striatum.
  • To determine if delta-opioid receptor agonists can modulate methamphetamine-induced changes in c-fos mRNA.
  • To explore the potential role of endogenous delta-opioid peptides in counteracting psychostimulant effects.

Main Methods:

  • Administration of methamphetamine to mice.
  • Systemic injection of the delta-opioid receptor agonist [D-Ala2, D-Leu5]enkephalin (DADLE).
  • Measurement of c-fos mRNA levels in the striatum using quantitative techniques.

Main Results:

  • Methamphetamine administration led to a significant increase in c-fos mRNA levels in the mouse striatum.
  • Systemic administration of DADLE attenuated the methamphetamine-induced increase in c-fos mRNA.
  • This indicates a modulatory effect of delta-opioid receptor activation on methamphetamine's genomic impact.

Conclusions:

  • Endogenous delta-opioid peptides may play a protective or counteracting role against the genomic effects of psychostimulants like methamphetamine.
  • Delta-opioid receptor signaling can influence the expression of immediate early genes like c-fos in response to drug exposure.
  • These findings contribute to understanding the complex neurobiological interactions between opioids and psychostimulants.

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