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Characterization of the decrease of extracellular striatal dopamine induced by intrastriatal morphine administration.

T P Piepponen1, J A Mikkola, M Ruotsalainen

  • 1Department of Pharmacy, University of Helsinki, Finland. petteri.piepponen@helsinki.fi

British Journal of Pharmacology
|June 16, 1999
PubMed
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Morphine directly inhibits dopamine release in the rat striatum via micro-opioid receptors, an effect that lessens with repeated drug exposure, indicating local tolerance development.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Morphine is known to stimulate the central nervous system.
  • Its local effects on dopamine release within the striatum are less understood.

Purpose of the Study:

  • To investigate the direct effect of intrastriatally administered morphine on striatal dopamine release in rats.
  • To determine the receptor mechanisms and tolerance development associated with this local effect.

Main Methods:

  • Reversed microdialysis was used to administer morphine directly into the rat striatum.
  • Extracellular concentrations of dopamine (DA) and its metabolites (DOPAC, HVA) were measured.
  • Effects of opioid receptor antagonists and agonists were assessed, along with repeated morphine administration.

Main Results:

Related Experiment Videos

  • Intrastriatal morphine dose-dependently decreased extracellular striatal dopamine levels.
  • This effect was blocked by naltrexone but not by a kappa-opioid antagonist, suggesting micro-opioid receptor involvement.
  • A selective micro-opioid agonist (DAMGO) mimicked morphine's effect.
  • Repeated morphine administration led to reduced dopamine decrease, indicating tolerance.

Conclusions:

  • Morphine exerts a local inhibitory effect on striatal dopamine release mediated by micro-opioid receptors.
  • Tolerance develops to this inhibitory action following repeated morphine administration.
  • These findings reveal a local inhibitory component to morphine's action on nigrostriatal dopamine neurons.