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Sensitization by ventral pallidal DAMGO: lack of cross-sensitization to morphine

Sandra L Rokosik1, Amanda L Persons, T Celeste Napier

  • 1Neuroscience Program, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.

Neuroreport
|January 23, 2013
PubMed

Insights

Repeated ventral pallidum injections of DAMGO, an opioid, caused long-lasting motor sensitization in rats. However, this DAMGO sensitization did not cross over to morphine, suggesting biased agonism at μ-opioid receptors.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Morphine administration into the ventral pallidum induces motor sensitization in rats.
  • Morphine and DAMGO ( [D-Ala, N-MePhe, Gly(ol)]-enkephalin ) activate μ-opioid receptors but may have differential signaling effects.

Purpose of the Study:

  • To investigate whether DAMGO and morphine differentially influence motor sensitization mediated by the ventral pallidum.
  • To explore the potential role of biased agonism in μ-opioid receptor-mediated behaviors.

Main Methods:

  • Repeated intraventral pallidal injections of DAMGO in laboratory rats.
  • Assessment of motor activity and sensitization development over time (at least 18 days).
  • Cross-sensitization challenges using morphine (intraventral pallidal or systemic) in DAMGO-sensitized rats.

Main Results:

  • Intraventral pallidal DAMGO injections induced robust and persistent motor sensitization.
  • No cross-sensitization was observed between DAMGO-induced sensitization and subsequent morphine challenges.
  • The motor response to morphine in DAMGO-sensitized rats was comparable to that of saline-treated controls.

Conclusions:

  • DAMGO induces long-lasting motor sensitization via ventral pallidal μ-opioid receptors.
  • The lack of cross-sensitization suggests that DAMGO and morphine engage distinct signaling pathways downstream of the μ-opioid receptor.
  • These findings support the concept of biased agonism, where different ligands acting on the same receptor can elicit distinct cellular and behavioral outcomes.

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