ArticleFrontiers in behavioral neuroscience2014
Behavioral architecture of opioid reward and aversion in C57BL/6 substrains.
Article in Frontiers in behavioral neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pain-related opioidergic and dopaminergic neurotransmission: Dual meta-Analyses of PET radioligand studies.Brain research · 2023Pooled it
- Genetic Modulation of Oxycodone Self-Administration Trajectories: From Initiation to Escalating Burst Patterns.bioRxiv : the preprint server for biology · 2026Article
- Genetic modulation of oxycodone self-administration trajectories: from initiation to escalating burst patterns.Frontiers in behavioral neuroscience · 2026Article
- Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.The Journal of pharmacology and experimental therapeutics · 2025Article
- Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains.Genes, brain, and behavior · 2025Article
- Article
- A master regulator of opioid reward in the ventral prefrontal cortex.Science (New York, N.Y.) · 2024Article
- Article
- Neuroimaging of opioid exposure: a review of preclinical animal models to inform addiction research.Psychopharmacology · 2023Review
- Cyfip2 allelic variation in C57BL/6J and C57BL/6NJ mice alters free-choice ethanol drinking but not binge-like drinking or wheel-running activity.Alcohol, clinical & experimental research · 2023Article
- Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.The Journal of pharmacology and experimental therapeutics · 2022Article
- Selective Inhibition of PDE4B Reduces Methamphetamine Reinforcement in Two C57BL/6 Substrains.International journal of molecular sciences · 2022Article
- Endogenous µ-opioid receptor activity in the lateral and capsular subdivisions of the right central nucleus of the amygdala prevents chronic postoperative pain.Journal of neuroscience research · 2022Article
- A quantitative trait variant in Gabra2 underlies increased methamphetamine stimulant sensitivity.Genes, brain, and behavior · 2021Article
- Supplier-origin mouse microbiomes significantly influence locomotor and anxiety-related behavior, body morphology, and metabolism.Communications biology · 2021Article
- Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.International journal of molecular sciences · 2021Article
- Substrains matter in phenotyping of C57BL/6 mice.Experimental animals · 2021Review
- Article
- Sex-dependent effects of an Hnrnph1 mutation on fentanyl addiction-relevant behaviors but not antinociception in mice.Genes, brain, and behavior · 2021Article
- Endogenous Opioid Signaling in the Mouse Retina Modulates Pupillary Light Reflex.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug liking vs. drug disliking is a subjective motivational measure in humans that assesses the addiction liability of drugs. Variation in this trait is hypothesized to influence vulnerability vs. resilience toward substance abuse disorders and likely contains a genetic component. In rodents and humans, conditioned place preference (CPP)/aversion (CPA) is a Pavlovian conditioning paradigm whereby a learned preference for the drug-paired environment is used to infer drug liking whereas a learned avoidance or aversion is used to infer drug disliking. C57BL/6 inbred mouse substrains are nearly genetically identical, yet demonstrate robust differences in addiction-relevant behaviors, including locomotor sensitization to cocaine and consumption of ethanol. Here, we tested the hypothesis that B6 substrains would demonstrate differences in the rewarding properties of the mu opioid receptor agonist oxycodone (5 mg/kg, i.p.) and the aversive properties of the opioid receptor antagonist naloxone (4 mg/kg, i.p.). Both substrains showed similar degrees of oxycodone-induced CPP; however, there was a three-fold enhancement of naloxone-induced CPA in agonist-naïve C57BL/6J relative to C57Bl/6NJ mice. Exploratory factor analysis of CPP and CPA identified unique factors that explain variance in behavioral expression of reward vs. aversion. "Conditioned Opioid-Like Behavior" was a reward-based factor whereby drug-free locomotor variables resembling opioid treatment co-varied with the degree of CPP. "Avoidance and Freezing" was an aversion-based factor, whereby the increase in the number of freezing bouts co-varied with the degree of aversion. These results provide new insight into the behavioral architecture of the motivational properties of opioids. Future studies will use quantitative trait locus mapping in B6 substrains to identify novel genetic factors that contribute to the marked strain difference in NAL-CPA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.