ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine β-hydroxylase.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 122 citations in OpenAlex.
- A randomized clinical trial of disulfiram at higher doses for the treatment of cocaine use disorder among methadone-stabilized patients.Journal of psychiatric research · 2025Trial
- The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals.Pharmacogenetics and genomics · 2016Trial
- Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.Psychiatry research · 2015Trial
- Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder.Progress in neuro-psychopharmacology & biological psychiatry · 2015Trial
- Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine.Progress in neuro-psychopharmacology & biological psychiatry · 2014Trial
- Pharmacogenetic randomized trial for cocaine abuse: disulfiram and α1A-adrenoceptor gene variation.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2013Trial
- The alpha-1 adrenergic antagonist doxazosin for treatment of cocaine dependence: A pilot study.Drug and alcohol dependence · 2013Trial
- Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylase.Biological psychiatry · 2013Trial
- Efficacy of disulfiram and Twelve Step Facilitation in cocaine-dependent individuals maintained on methadone: a randomized placebo-controlled trial.Drug and alcohol dependence · 2012Trial
- The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial.PloS one · 2012Trial
- Noradrenergic α₁ receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial.PloS one · 2012Trial
- Effects of disulfiram on QTc interval in non-opioid-dependent and methadone-treated cocaine-dependent patients.Journal of addiction medicineTrial
- The role of polysubstance use in the development, maintenance, and treatment of stimulant use disorders.Pharmacological reviews · 2026Review
- Exposure to disulfiram and incidence of parkinsonism.Journal of occupational medicine and toxicology (London, England) · 2025Article
- Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.Microbial biotechnology · 2025Article
- Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice.Neurobiology of stress · 2024Article
- Genetic disruption of dopamine β-hydroxylase dysregulates innate responses to predator odor in mice.bioRxiv : the preprint server for biology · 2024Article
- Chronic administration of a norepinephrine antagonist prevents and partially reverses escalation of cocaine self-administration.Addiction biology · 2023Article
- Effects of sex and estrous cycle on intravenous oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats.bioRxiv : the preprint server for biology · 2023Article
- Disulfiram: Mechanisms, Applications, and Challenges.Antibiotics (Basel, Switzerland) · 2023Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive 'Antabuse reaction' that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use, even in the absence of an interaction with alcohol, indicating the existence of an ALDH-independent therapeutic mechanism. We hypothesized that disulfiram's inhibition of dopamine β-hydroxylase (DBH), the catecholamine biosynthetic enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons, underlies the drug's ability to treat cocaine dependence. We tested the effects of disulfiram on cocaine and food self-administration behavior and drug-primed reinstatement of cocaine seeking in rats. We then compared the effects of disulfiram with those of the selective DBH inhibitor, nepicastat. Disulfiram, at a dose (100 mg/kg, i.p.) that reduced brain NE by ∼40%, did not alter the response for food or cocaine on a fixed ratio 1 schedule, whereas it completely blocked cocaine-primed (10 mg/kg, i.p.) reinstatement of drug seeking following extinction. A lower dose of disulfiram (10 mg/kg) that did not reduce NE had no effect on cocaine-primed reinstatement. Nepicastat recapitulated the behavioral effects of disulfiram (100 mg/kg) at a dose (50 mg/kg, i.p.) that produced a similar reduction in brain NE. Food-primed reinstatement of food seeking was not impaired by DBH inhibition. Our results suggest that disulfiram's efficacy in the treatment of cocaine addiction is associated with the inhibition of DBH and interference with the ability of environmental stimuli to trigger relapse.
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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.