Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats

Townsend, E. Andrew; Naylor, Jennifer E.; Negus, S. Stevens; Edwards, Shelley R.; Qureshi, Hina N.; McLendon, Hunter W.; McCurdy, Christopher R.; Kapanda, Coco N.; Carmo, Jussara M. do; Silva, Fernanda S. da; Hall, John E.; Sufka, Kenneth J.; Freeman, Kevin B.

doi:10.1007/s00213-017-4652-3

Cited by 51 publications

(58 citation statements)

References 30 publications

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“…The acquisition in the males was consistent with that observed using similar procedures in a group of experimentally naïve adult males (Nguyen et al, 2019). Unfortunately the majority of rat oxycodone IVSA studies published so far have been in male rats (Austin Zamarripa et al, 2018;Blackwood et al, 2019;Bossert et al, 2018;Jordan et al, 2019;Leri and Burns, 2005;Mavrikaki et al, 2019;Nawarawong et al, 2018;Neelakantan et al, 2017;Nguyen et al, 2019;Nguyen, J. D. et al, 2018b;Pravetoni et al, 2014;Townsend et al, 2017;Wade et al, 2015;You et al, 2018;You et al, 2017); one exception was a study in pregnant rats (Vassoler et al, 2018). Interestingly, when female animals were evaluated on a fentanyl dose substitution under an FR procedure, the THC exposed rats self-administered more drug at the lowest dose (Figure 9).…”

Section: Discussionsupporting

confidence: 81%

Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

Nguyen

Creehan

Kerr

et al. 2018

Preprint

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Adolescents are regularly exposed to ∆ 9 -tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference.Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl selfadministration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood.

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Section: Discussionsupporting

confidence: 81%

Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

Nguyen

Creehan

Kerr

et al. 2018

Preprint

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“…Our study is in line with growing research into the development of biased KOP-r ligands for anti-addictive compounds [Maillet et al, 2015;White et al, 2015;Brust et al, 2016;Townsend et al, 2017].…”

Section: Kappa Opioid Receptor (Kop-r) and Dynorphin Systemsupporting

confidence: 82%

“…Recently, there is rapidly growing research into the identification of functionally selective (biased) KOP-r full agonists or partial agonists for the development of anti-addictive compounds [Maillet et al, 2015;Simonson et al, 2015;White et al, 2015;Brust et al, 2016;Schattauer et al, 2017;Townsend et al, 2017;Zhou et al, 2017a]. For a good example, Mesyl Salvinorin B (MSB), an analogue of salvinorin A, is a potent KOP-r full agonist with fewer side effects (sedation and dysphoria) compared to other "classic" KOP-r agonists [Simonson et al, 2015;Zhou et al, 2017a].…”

Section: Kappa Opioid Receptor (Kop-r) and Dynorphin Systemmentioning

confidence: 99%

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Zhou

Kreek

2018

J Pharmacol Exp Ther

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Addiction to specific drugs (such as alcohol, psychostimulants and opioids) shares some common direct or downstream effects on the brain stress-responsive systems, including arginine vasopressin and its V1b receptors, dynorphin and the kappa opioid receptors, proopiomelanocortin/β-endorphin and the mu opioid receptors, and the endocannabinoids. Further study of these systems, through laboratory-based and translational research, could lead to the discovery of novel treatment targets and the early optimization of interventions (for example, combination) for the pharmacological therapy of alcoholism.

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“…However, in light of the current prescription opioid epidemic, we recently changed our focus to studying relapse to oxycodone, a prototypical prescription opioid drug that is widely used for pain management (Van Zee, 2009;Yaksh & Wallace, 2011). We also chose to study oxycodone because compared to heroin (Wise, 1989;Koob, 1992;Badiani et al, 2011;Bossert et al, 2013), there are very few published studies on oxycodone self-administration and relapse/reinstatement (Leri & Burns, 2005;Campbell et al, 2012;Pravetoni et al, 2014;Secci et al, 2016;Neelakantan et al, 2017;Townsend et al, 2017;You et al, 2017). Human and rodent binding studies show that oxycodone is a preferential mu opioid receptor (MOR) agonist (Lalovic et al, 2006;Peckham & Traynor, 2006) with lower affinity to MOR than morphine (Lalovic et al, 2006;Peckham & Traynor, 2006); there is also evidence that oxycodone binds to the kappa opioid receptor (KOR) (Nielsen et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Role of mu, but not delta or kappa, opioid receptors in context‐induced reinstatement of oxycodone seeking

Bossert

Hoots

Fredriksson

et al. 2018

Eur J of Neuroscience

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Relapse to non-medical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/day in context A; lever pressing was paired with a discrete cue. Next, we extinguished the lever pressing in the presence of the discrete cue in context B and then tested the rats for reinstatement of oxycodone seeking in both contexts. We retrained rats to self-administer oxycodone in context A, re-extinguished their lever pressing in context B and retested them for reinstatement in both contexts. Prior to testing, we injected the rats with vehicle or antagonists of MOR (naltrexone; 0.5 or 1.0 mg/kg), DOR (naltrindole; 7.5 or 15 mg/kg) or KOR (LY2456302; 5 or 10 mg/kg). We also tested the effect of naltrexone, naltrindole and LY2456302 on oxycodone self-administration under fixed-ratio-1 (FR1) and progressive ratio (PR) reinforcement schedules. We observed context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction. Naltrexone, but not naltrindole or LY2456302, injections decreased this reinstatement. Additionally, naltrexone increased oxycodone self-administration under the FR1 schedule and decreased oxycodone self-administration under the PR schedule; naltrindole and LY2456302 were ineffective. Results demonstrate a critical role of MOR, but not DOR or KOR, in context-induced reinstatement of oxycodone seeking and oxycodone self-administration.

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Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats

Cited by 51 publications

References 30 publications

Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Role of mu, but not delta or kappa, opioid receptors in context‐induced reinstatement of oxycodone seeking

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