Activation of delta-opioid receptor contributes to the antinociceptive effect of oxycodone in mice

Yang, Pao Pao; Yeh, Geng Chang; Yeh, Teng Kuang; Xi, Jingchao; Loh, Horace H.; Law, Ping Yee; Tao, Pao‐Luh

doi:10.1016/j.phrs.2016.05.034

Cited by 29 publications

(19 citation statements)

References 39 publications

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“…As the analgesic effects of oxycodone may be non-specific ( Yang et al, 2016 ), we first examined the locomotor effect of oxycodone (10 mg/kg, s.c.) in mice lacking MORs in all cells, a global MOR KO, and their WT littermates, ( Fig. 2 A ) over three consecutive days.…”

Section: Resultsmentioning

confidence: 99%

μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors

Severino

Mittal

Hakimian

et al. 2020

eNeuro

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μ-Opioid receptors (MORs) are densely expressed in different brain regions known to mediate reward. One such region is the striatum where MORs are densely expressed, yet the role of these MOR populations in modulating reward is relatively unknown. We have begun to address this question by using a series of genetically engineered mice based on the Cre recombinase/loxP system to selectively delete MORs from specific neurons enriched in the striatum: dopamine 1 (D1) receptors, D2 receptors, adenosine 2a (A2a) receptors, and choline acetyltransferase (ChAT). We first determined the effects of each deletion on opioid-induced locomotion, a striatal and dopamine-dependent behavior. We show that MOR deletion from D1 neurons reduced opioid (morphine and oxycodone)-induced hyperlocomotion, whereas deleting MORs from A2a neurons resulted in enhanced opioid-induced locomotion, and deleting MORs from D2 or ChAT neurons had no effect. We also present the effect of each deletion on opioid intravenous self-administration. We first assessed the acquisition of this behavior using remifentanil as the reinforcing opioid and found no effect of genotype. Mice were then transitioned to oxycodone as the reinforcer and maintained here for 9 d. Again, no genotype effect was found. However, when mice underwent 3 d of extinction training, during which the drug was not delivered, but all cues remained as during the maintenance phase, drug-seeking behavior was enhanced when MORs were deleted from A2a or ChAT neurons. These findings show that these selective MOR populations play specific roles in reward-associated behaviors.

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Section: Resultsmentioning

confidence: 99%

μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors

Severino

Mittal

Hakimian

et al. 2020

eNeuro

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“…Yang et al . () had reported that in μ receptor knockout mice, high doses of oxycodone (>40 mg·kg −1 s.c.) induce naltrindole‐reversible antinociception.…”

Section: Discussionmentioning

confidence: 99%

Oxycodone‐induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition

Hill

Dewey

Kelly

et al. 2018

British J Pharmacology

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BACKGROUND AND PURPOSEOxycodone, a prescription opioid, is a major drug of abuse, especially in the USA, and contributes significantly to opioid overdose deaths each year. Overdose deaths result primarily from respiratory depression. We have studied respiratory depression by oxycodone and have characterized how tolerance develops on prolonged exposure to the drug. We have investigated the role of PKC in maintaining tolerance and have examined whether ethanol or pregabalin reverses oxycodoneinduced tolerance. EXPERIMENTAL APPROACHRespiration was measured in male CD-1 mice by whole-body plethysmography. Mice were preinjected with oxycodone then implanted with mini-pumps (s.c.) delivering 20, 45 or 120 mg·kg À1 ·day À1 oxycodone for 6 days and subsequently challenged with oxycodone (3 mg·kg À1 , i.p.) or morphine (10 mg·kg À1 , i.p.) to assess the level of tolerance. KEY RESULTSOxycodone-treated mice developed tolerance to oxycodone and cross tolerance to morphine-induced respiratory depression. Tolerance was less with 20 mg·kg À1 ·day À1 than with 45 or 120 mg·kg À1 ·day À1 oxycodone treatment. At doses that do not depress respiration, ethanol (0.3 g·kg À1 ), pregabalin (20 mg·kg À1 ) and calphostin C (45 μg·kg À1 ) all reversed oxycodone-induced tolerance resulting in significant respiratory depression. Reversal of tolerance was less in mice treated with oxycodone (120-mg·kg À1 ·day À1 ). In mice receiving ethanol and calphostin C or ethanol and pregabalin, there was no greater reversal of tolerance than seen with either drug alone. CONCLUSION AND IMPLICATIONSThese data suggest that oxycodone-induced tolerance is mediated by PKC and that reversal of tolerance by ethanol or pregabalin may be a contributory factor in oxycodone overdose deaths. Abbreviation NorBNI, norbinaltorphimineBritish Journal of

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“…To achieve these goals, we have measured the mRNA and protein expression of the three opioid receptors in these two brain regions that express the three receptors [ 27 – 29 ]. Parenthetically, oxycodone has also been reported to interact with the three relevant opioid receptor proteins [ 30 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration

et al. 2018

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Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Here, we sought to identify potential neurobiological consequences of withdrawal from escalated and non-escalated oxycodone self-administration in rats. To reach these goals, we used short-access (ShA) (3 h) and long-access (LgA) (9 h) exposure to oxycodone self-administration followed by protracted forced abstinence. After 31 days of withdrawal, we quantified mRNA and protein levels of opioid receptors in the rat dorsal striatum and hippocampus. Rats in the LgA, but not the ShA, group exhibited escalation of oxycodone SA, with distinction of two behavioral phenotypes of relatively lower (LgA-L) and higher (LgA-H) oxycodone takers. Both LgA, but not ShA, phenotypes showed time-dependent increases in oxycodone seeking during the 31 days of forced abstinence. Rats from both LgA-L and LgA-H groups also exhibited decreased levels of striatal mu opioid receptor protein levels in comparison to saline and ShA rats. In contrast, mu opioid receptor mRNA expression was increased in the dorsal striatum of LgA-H rats. Moreover, hippocampal mu and kappa receptor protein levels were both increased in the LgA-H phenotype. Nevertheless, hippocampal mu receptor mRNA levels were decreased in the two LgA groups whereas kappa receptor mRNA expression was decreased in ShA and LgA oxycodone groups. Decreases in striatal mu opioid receptor protein expression in the LgA rats may serve as substrates for relapse to drug seeking because these changes occur in rats that showed incubation of oxycodone seeking.

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Activation of delta-opioid receptor contributes to the antinociceptive effect of oxycodone in mice

Cited by 29 publications

References 39 publications

μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors

μ-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors

Oxycodone‐induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition

Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration

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