Compulsive-Like Responding for Opioid Analgesics in Rats with Extended Access

Wade, Carrie L.; Vendruscolo, Leandro F.; Schlosburg, Joel E.; Hernandez, Daniel O; Koob, George F.

doi:10.1038/npp.2014.188

Cited by 137 publications

(137 citation statements)

References 32 publications

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“…in adult mice (Zhang et al, 2009). In rats, a similar decrease in number of oxycodone infusions and an increase in total intake was found in an intravenous self-administration procedure examining duration of drug access (Wade et al, 2015). Differences in these reported patterns of self-administered oxycodone might be a function of the range of doses and concentrations tested, in that the ascending limb of the dose-effect curve may be missed if doses not low enough are untested.…”

Section: Discussionmentioning

confidence: 55%

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice

Enga

Jackson

Damaj

et al. 2016

European Journal of Pharmacology

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Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone’s antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056–1.0 mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0–33.0 mg/kg, s.c.) over 9 days, challenged with naloxone (0.1–10.0 mg/kg, s.c.), and then observed for 30 min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid.

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Section: Discussionmentioning

confidence: 55%

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice

Enga

Jackson

Damaj

et al. 2016

European Journal of Pharmacology

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“…Common procedures for the induction of opioid dependence include intravenous self-administration of opioids (Unite 9.20) (Thomsen & Caine, 2005) and subcutaneous administration (Park et al, 2015; Pahng et al, 2017). Intravenous self-administration (12-hr access) of fentanyl (2.5μg/kg/infusion; 5mg/kg/infusion), oxycodone (150μg/kg/infusion; 300μg/kg/infusion) , and heroin ( 60μg/kg/infusion) , but not buprenorphine produces a robust escalation of opioid intake (Wade et al, 2015). Intravenous self-administration (12-hr access) of heroin ( 0.06mg/kg/infusion) produces hyperalgesia (Edwards et al, 2012b).…”

Section: Support Protocol 2: Alcohol- and Morphine-dependence Inductimentioning

confidence: 99%

Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats

Pahng

Edwards

2018

CP Neuroscience

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In contrast to their analgesic properties, excessive use of either opioids or alcohol produces a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may promote increased use of opioids or alcohol drinking to manage worsening pain symptoms. Hyperalgesia has traditionally been measured in rodents via reflex-based assays, including the von Frey method. To better model the motivational and affective dimensions of pain in a state of opioid/alcohol dependence and withdrawal, this unit describes the use of a non-reflex-based method for measuring pain avoidance-like behavior in dependent rats. In the mechanical conflict-avoidance task, rats run across probes of varying heights to avoid a bright aversive light and to reach a dark goal chamber. A longer latency to exit onto the nociceptive probes reflects increased pain avoidance-like behavior during withdrawal. Mechanical conflict-avoidance testing can be repeated to provide both baseline assessment of pain avoidance behavior and pain avoidance measures after the induction of dependence.

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“…44–46 Oxycodone is self-administered by rats and monkeys, and its reinforcing effects are blocked by μ-opioid antagonists (e.g., naltrexone). 47–51 In the present study, we trained rats to self-administer oxycodone (0.1 mg/kg/infusion) and investigated the hypothesis that lorcaserin would suppress intake of oxycodone and cue reactivity in rats. Lorcaserin is a high-affinity, full agonist at the human 5-HT 2C R with selectivity over the 5-HT 2A R (18-fold) and 5-HT 2B R (104-fold), sites at which lorcaserin is a partial and full agonist, respectively.…”

Section: Introductionmentioning

confidence: 99%

Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats

Neelakantan

Holliday

Fox

et al. 2017

ACS Chem. Neurosci.

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Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses (“cue reactivity”) that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is FDA-approved for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats. We found that lorcaserin inhibited oxycodone intake, an effect blocked by the selective 5-HT2CR antagonist SB242084. Lorcaserin also decreased responding for the discrete cue complex (“cue reactivity”) previously associated with delivery of oxycodone (i.e., stimulus lights, infusion pump sounds) in both abstinence and extinction-reinstatement models. The selected dose range of lorcaserin (0.25–1 mg/kg) does not overtly alter spontaneous behaviors nor operant responding on inactive levers in the present study. Taken together, the ability of lorcaserin to reduce the oxycodone self-administration and decrease cue reactivity associated with relapse highlights the therapeutic potential for lorcaserin in the treatment of OUD.

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Compulsive-Like Responding for Opioid Analgesics in Rats with Extended Access

Cited by 137 publications

References 32 publications

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice

Oxycodone physical dependence and its oral self-administration in C57BL/6J mice

Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats

Lorcaserin Suppresses Oxycodone Self-Administration and Relapse Vulnerability in Rats

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