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Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors.

ABSTRACT: The exact role of delta opioid receptors in drug-induced conditioned place preference (CPP) remains debated. Under classical experimental conditions, morphine-induced CPP is decreased in mice lacking delta opioid receptors (Oprd1 (-/-)). Morphine self-administration, however, is maintained, suggesting that drug-context association rather than drug reward is deficient in these animals.This study further examined the role of delta opioid receptors in mediating drug-cue associations, which are necessary for the expression of morphine-induced CPP.We first identified experimental conditions under which Oprd1 (-/-) mice are able to express CPP to morphine (5, 10 or 20 mg/kg) in a drug-free state and observed that, in this paradigm, CPP was dependent on circadian time conditions. We then took advantage of this particularity to assess the ability of various cues (internal or discrete), predicting either drug or food reward, to restore CPP induced by morphine (10 mg/kg) in Oprd1 (-/-) mice in conditions under which they normally fail to express CPP.We found that presentation of circadian, drug or auditory cues, predicting morphine or food reward, restored morphine CPP in Oprd1 (-/-) mice, which then performed as well as control mice.This study reveals that, in contrast to spatial cues, internal or discrete morphine-predicting stimuli permit full expression of morphine CPP in Oprd1 (-/-) mice. Delta receptors, therefore, appear to play a crucial role in modulating spatial contextual cue-related responses. This activity may be critical when context gains control over behavior, as is the case for context-induced relapse in drug abuse.

SUBMITTER: Le Merrer J

PROVIDER: S-EPMC5632531 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors.

Le Merrer Julie J Faget Lauren L Matifas Audrey A Kieffer Brigitte L BL

Psychopharmacology 20120418 1

<h4>Rationale</h4>The exact role of delta opioid receptors in drug-induced conditioned place preference (CPP) remains debated. Under classical experimental conditions, morphine-induced CPP is decreased in mice lacking delta opioid receptors (Oprd1 (-/-)). Morphine self-administration, however, is maintained, suggesting that drug-context association rather than drug reward is deficient in these animals.<h4>Objectives</h4>This study further examined the role of delta opioid receptors in mediating ...[more]

PMID: 22526530

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Project description:BackgroundPersistent use of prescription opioids beyond the period of surgical recovery is a large part of a public health problem linked to the current opioid crisis in the United States. However, few studies have been conducted to examine whether morphine reward is influenced by acute pain and injury.MethodsIn a mouse model of incisional injury and minor trauma, animals underwent conditioning, extinction, and drug-primed reinstatement with morphine to examine the rewarding properties of morphine in the presence of acute incisional injury and drug-induced relapse, respectively. In addition, we sought to determine whether these behaviors were influenced by kappa opioid receptor signaling and measured expression of prodynorphin messenger RNA in the nucleus accumbens and medial prefrontal cortex after conditioning and before reinstatement with morphine and incisional injury.ResultsIn the presence of incisional injury, we observed enhancement of morphine reward with morphine-conditioned place preference but attenuated morphine-primed reinstatement to reward. This adaptation was not present in animals conditioned 12 days after incisional injury when nociceptive sensitization had resolved; however, they showed enhancement of morphine-primed reinstatement. Prodynorphin expression was greatly enhanced in the nucleus accumbens and medial prefrontal cortex of mice with incisional injury and morphine conditioning and remained elevated up to drug-primed reinstatement. These changes were not observed in mice conditioned 12 days after incisional injury. Further, kappa opioid receptor blockade with norbinaltorphimine before reinstatement reversed the attenuation induced by injury.ConclusionsThese findings suggest enhancement of morphine reward as a result of incisional injury but paradoxically a protective adaptation with incisional injury from drug-induced relapse resulting from kappa opioid receptor activation in the reward circuitry. Remote injury conferred no such protection and appeared to enhance reinstatement.

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Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors.

Publications

Cues predicting drug or food reward restore morphine-induced place conditioning in mice lacking delta opioid receptors.

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