ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Pharmacokinetics trumps pharmacodynamics during cocaine choice: a reconciliation with the dopamine hypothesis of addiction.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
- Conditioned accumbal dopamine transients forecast individual preference for drug versus natural rewards and compulsive behavior.Nature neuroscience · 2026Article
- Characterization of Neuronal Ensembles in a Model of Dual-Reward Conditioned Place Preference.eNeuro · 2026Article
- Assessing behavioral reallocation after acute environmental manipulations using an asymmetric cocaine versus sucrose choice task in male and female rats.Psychopharmacology · 2026Article
- Assessing behavioral reallocation after acute environmental manipulations using an asymmetric cocaine versus sucrose choice task in male and female rats.Research square · 2025Article
- A preliminary study of the physiological and perceptual effects of GLP-1 receptor agonists during alcohol consumption in people with obesity.Scientific reports · 2025Article
- Mechanistic and translational insights from preclinical cocaine choice procedures on the economic substitutability of cocaine and nondrug reinforcers.Neuroscience and biobehavioral reviews · 2025Review
- Formation of an Enduring Ensemble of Accumbens Neurons Leads to Prepotent Seeking for Cocaine Over Natural Reward Cues.bioRxiv : the preprint server for biology · 2024Article
- The importance of choice and agency in animal models of addiction.Journal of neural transmission (Vienna, Austria : 1996) · 2024Article
- Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.Experimental and clinical psychopharmacology · 2024Article
- Acquisition of cocaine reinforcement using fixed-ratio and concurrent choice schedules in socially housed female and male monkeys.Psychopharmacology · 2024Article
- Neural circuits controlling choice behavior in opioid addiction.Neuropharmacology · 2023Review
- Rats choose alcohol over social reward in an operant choice procedure.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Protective Effect of Social Reward on Opioid and Psychostimulant Reward and Relapse: Behavior, Pharmacology, and Brain Regions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Individual differences in cocaine seeking during voluntary abstinence predicts cocaine relapse and the circuitry mediating relapse.Psychopharmacology · 2022Article
- The impact of caloric availability on eating behavior and ultra-processed food reward.Appetite · 2022Article
- Oxytocin and orexin systems bidirectionally regulate the ability of opioid cues to bias reward seeking.Translational psychiatry · 2022Article
- Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward.Molecular psychiatry · 2022Article
- Characterization of operant social interaction in rats: effects of access duration, effort, peer familiarity, housing conditions, and choice between social interaction vs. food or remifentanil.Psychopharmacology · 2022Article
- Mile high on heroin: Lessons on the opioid epidemic from the Mile High City.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this abnormally large dopamine response would explain why cocaine use is initially highly rewarding and addictive. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative. Here we report evidence that reconciles this finding with the dopamine hypothesis of addiction. First, a systematic literature analysis revealed that the delays of effects of intravenous cocaine on nucleus accumbens dopamine are of the order of tens of seconds and are considerably longer than those of nondrug reward. Second, this was confirmed by measuring response times to cocaine omission during self-administration as a behavioral proxy of these delays. Finally, when the influence of the drug delays was reduced during choice by adding an increasing delay to both the drug and nondrug rewards, rats shifted their choice to cocaine. Overall, this study suggests that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics.
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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.