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
delta-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
delta-opioid receptor in
morphine-induced conditioned responses by examining the effect of a selective delta2-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 mu-
opioid and
delta-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
delta-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 mu-opoid receptor in the total homogenate. Overall, these results suggest that modulation of the
delta-opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt
morphine-induced conditioned responses.