Disruption of morphine-conditioned place preference by a δ2-opioid receptor antagonist: Study of μ-opioid and δ-opioid receptor expression at the synapse

Sophie K. Billa, Yan Xia, Jose A. Morón

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the δ-opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ-opioid receptor in morphine-induced conditioned responses by examining the effect of a selective δ2-opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ-opioid and δ-opioid receptors in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine-induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine-induced conditioned place preference. Interestingly, this naltriben-induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ-opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ-opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ-opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine-induced conditioned responses.

Original languageEnglish
Pages (from-to)625-631
Number of pages7
JournalEuropean Journal of Neuroscience
Volume32
Issue number4
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Keywords

  • Conditioned place preference (CPP)
  • Hippocampus
  • Morphine
  • Rat
  • Receptor
  • δ-opioid receptor

Fingerprint Dive into the research topics of 'Disruption of morphine-conditioned place preference by a δ2-opioid receptor antagonist: Study of μ-opioid and δ-opioid receptor expression at the synapse'. Together they form a unique fingerprint.

  • Cite this