Lack of effect of different pain-related manipulations on opioid self-administration, reinstatement of opioid seeking, and opioid choice in rats

Reiner, David J.; Townsend, E. Andrew; Orihuel, Javier; Applebey, Sarah V.; Claypool, Sarah M; Banks, Matthew L.; Shaham, Yavin; Negus, S. Stevens

doi:10.1007/s00213-021-05816-9

Cited by 20 publications

(8 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This article is intended solely for the personal use of the individual user and is not to be disseminated broadly. DRUG AND NONDRUG REINFORCER INTERACTIONS reinforcement (Reiner et al, 2021) or even that pain reduces opioid reinforcement (for review, see Nazarian et al, 2021). The choice model used here, where rats chose between an opioid and safety from shock at varying prices, may better capture the relation between opioid taking and pain.…”

Section: Discussionmentioning

confidence: 99%

“…A hypothesis often tested, explicitly or implicitly, by these models is that pain should increase the reinforcing effects of opioids. But recent experiments in animals have found no effect of pain on opioid reinforcement (Reiner et al, 2021) or even that pain reduces opioid reinforcement (for review, see Nazarian et al, 2021). The choice model used here, where rats chose between an opioid and safety from shock at varying prices, may better capture the relation between opioid taking and pain.…”

Section: Discussionmentioning

confidence: 99%

“…Animal models have thus far had difficulty capturing the relation between opioids and pain that is thought to promote opioid taking in humans (Nazarian et al, 2021; Reiner et al, 2021). A hypothesis often tested, explicitly or implicitly, by these models is that pain should increase the reinforcing effects of opioids.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

Beasley,

Amantini,

Gunawan

et al. 2024

Experimental and Clinical Psychopharmacology

View full text Add to dashboard Cite

The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)-that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. Public Health SignificanceThe present study used a rat model to test how the availability of different nondrug alternatives impact the taking of cocaine and heroin. The results could help in understanding factors that promote or reduce the use of these drugs in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

Beasley,

Amantini,

Gunawan

et al. 2024

Experimental and Clinical Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…These findings indicate that the persistence of pain is an important driver of opioid consumption. Adding further support to this, acute pain manipulations with capsaicin or lactic acid do not alter rates of fentanyl or heroin self-administration, but persistent inflammatory pain-induced reductions in fentanyl vs. food choice procedures match controls by one week after the induction of pain ( Reiner et al, 2021 ). Notably, a small study found that arthritic pain reduced self-administration of relatively high doses of morphine with 24-h access for weeks following pain onset ( Lyness et al, 1989 ) while another found that multiple forms of chronic pain attenuated oral fentanyl self-administration and discrimination in mice ( Wade et al, 2013 ).…”

Section: Opioid System Dysfunction By Exogenous Opioidsmentioning

confidence: 92%

Endogenous opioid systems alterations in pain and opioid use disorder

Higginbotham

Markovic

Massaly

et al. 2022

Front. Syst. Neurosci.

View full text Add to dashboard Cite

Decades of research advances have established a central role for endogenous opioid systems in regulating reward processing, mood, motivation, learning and memory, gastrointestinal function, and pain relief. Endogenous opioid systems are present ubiquitously throughout the central and peripheral nervous system. They are composed of four families, namely the μ (MOPR), κ (KOPR), δ (DOPR), and nociceptin/orphanin FQ (NOPR) opioid receptors systems. These receptors signal through the action of their endogenous opioid peptides β-endorphins, dynorphins, enkephalins, and nociceptins, respectfully, to maintain homeostasis under normal physiological states. Due to their prominent role in pain regulation, exogenous opioids—primarily targeting the MOPR, have been historically used in medicine as analgesics, but their ability to produce euphoric effects also present high risks for abuse. The ability of pain and opioid use to perturb endogenous opioid system function, particularly within the central nervous system, may increase the likelihood of developing opioid use disorder (OUD). Today, the opioid crisis represents a major social, economic, and public health concern. In this review, we summarize the current state of the literature on the function, expression, pharmacology, and regulation of endogenous opioid systems in pain. Additionally, we discuss the adaptations in the endogenous opioid systems upon use of exogenous opioids which contribute to the development of OUD. Finally, we describe the intricate relationship between pain, endogenous opioid systems, and the proclivity for opioid misuse, as well as potential advances in generating safer and more efficient pain therapies.

show abstract

“…Abuse Liability Studies. 63,72,73 Rats were initially trained to respond for IV heroin (32 μg/kg/infusion) under a FR 5/time out 20 s schedule of reinforcement during daily 2 h sessions. Drug availability was signaled by the illumination of the chamber house light and extension of both levers.…”

Section: ■ Methodsmentioning

confidence: 99%

Preclinical Characterization and Development on NAQ as a Mu Opioid Receptor Partial Agonist for Opioid Use Disorder Treatment

Pagare

Obeng

Huang

et al. 2022

ACS Pharmacol. Transl. Sci.

Self Cite

View full text Add to dashboard Cite

Mu opioid receptor (MOR) selective antagonists and partial agonists have clinical utility for the treatment of opioid use disorders (OUDs). However, the development of many has suffered due to their poor pharmacokinetic properties and/or rapid metabolism. Our recent efforts to identify MOR modulators have provided 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3-carboxamido)morphinan (NAQ), a low-efficacy partial agonist, that showed sub-nanomolar binding affinity to the MOR (K i 0.6 nM) with selectivity over the delta opioid receptor (δ/μ 241) and the kappa opioid receptor (κ/μ 48). Its potent inhibition of the analgesic effect of morphine (AD50 0.46 mg/kg) and precipitation of significantly less withdrawal symptoms even at 100-fold greater dose than naloxone represents a promising molecule for further development as a novel OUD therapeutic agent. Therefore, further in vitro and in vivo characterization of its pharmacokinetics and pharmacodynamics properties was conducted to fully understand its pharmaceutical profile. NAQ showed favorable in vitro ADMET properties and no off-target binding to several classes of GPCRs, enzymes, and ion channels. Following intravenous administration, 1 mg/kg dose of NAQ showed a similar in vivo pharmacokinetic profile to naloxone; however, orally administered 10 mg/kg NAQ demonstrated significantly improved oral bioavailability over both naloxone and naltrexone. Abuse liability assessment of NAQ in rats demonstrated that NAQ functioned as a less potent reinforcer than heroin. Chronic 5 day NAQ pretreatment decreased heroin self-administration in a heroin-vs-food choice procedure similar to the clinically used MOR partial agonist buprenorphine. Taken together, these studies provide evidence supporting NAQ as a promising lead to develop novel OUD therapeutics.

show abstract

Lack of effect of different pain-related manipulations on opioid self-administration, reinstatement of opioid seeking, and opioid choice in rats

Cited by 20 publications

References 79 publications

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

Endogenous opioid systems alterations in pain and opioid use disorder

Preclinical Characterization and Development on NAQ as a Mu Opioid Receptor Partial Agonist for Opioid Use Disorder Treatment

Contact Info

Product

Resources

About