ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
The selective dopamine β-hydroxylase inhibitor nepicastat attenuates multiple aspects of cocaine-seeking behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
49 citing papers in PubMed, 81 citations in OpenAlex.
- The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals.Pharmacogenetics and genomics · 2016Trial
- 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
- Designing chemigenetic DNA nanotrap for norepinephrine dynamic imaging in organelles.Nature chemical biology · 2026Article
- The autism-linked gut microbial metabolite p-cresol inhibits host catecholamine biosynthesizing enzymes to elicit social deficits.Communications biology · 2025Article
- Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats.Addiction neuroscience · 2025Article
- Exploring Nepicastat Activity: Beyond DβH.International journal of molecular sciences · 2025Article
- Article
- 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
- Effects of sex and estrous cycle on intravenous oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats.Frontiers in behavioral neuroscience · 2023Article
- Norepinephrine and dopamine contribute to distinct repetitive behaviors induced by novel odorant stress in male and female mice.Hormones and behavior · 2022Article
- Noradrenergic circuits and signaling in substance use disorders.Neuropharmacology · 2022Review
- A role for cortical dopamine in the paradoxical calming effects of psychostimulants.Scientific reports · 2022Article
- Acute inhibition of dopamine β-hydroxylase attenuates behavioral responses to pups in adult virgin California mice (Peromyscus californicus).Hormones and behavior · 2022Article
- Treatment with dopamine β-hydroxylase (DBH) inhibitors prevents morphine use and relapse-like behavior in rats.Pharmacological reports : PR · 2021Article
- Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking.Neurobiology of stress · 2021Review
- Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking.Journal of neurochemistry · 2021Review
- Noradrenergic circuits in the forebrain control affective responses to novelty.Psychopharmacology · 2020Article
- Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder.Psychopharmacology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Although norepinephrine (NE) does not typically modulate cocaine self-administration under traditional schedules of reinforcement, it is required for different inducers of the reinstatement of cocaine-seeking behavior via activation of multiple adrenergic receptor subtypes. We predicted that blockade of NE synthesis would attenuate all known modalities of reinstatement and showed previously that the selective dopamine β-hydroxylase inhibitor, nepicastat, had no effect on either maintenance of operant cocaine self-administration maintained on a fixed-ratio 1 schedule or reinstatement of food seeking but did abolish cocaine-primed reinstatement. In the present series of studies, we first evaluated the dose-dependent effect of nepicastat (5, 50, or 100 mg/kg) on novelty-induced locomotor activity and found that it blunted exploration only at the highest dose. Next, we assessed the ability of nepicastat (50 mg/kg) to reduce breakpoint responding for cocaine on a progressive ratio schedule and reinstatement induced by drug-associated cues and stress. We found that nepicastat significantly lowered the breakpoint for cocaine, but not for regular chow or sucrose, and attenuated cue-, footshock-, and yohimbine-induced reinstatement. Combined, these results indicate that nepicastat can reduce the reinforcing properties of cocaine under a stringent schedule and can attenuate relapse-like behavior produced by cocaine, formerly cocaine-paired cues, and physiological and pharmacological stressors. Thus, nepicastat is one of those rare compounds that can reduce reinforced cocaine seeking as well as all three reinstatement modalities, while sparing exploratory behavior and natural reward seeking, making it a promising pharmacotherapy for cocaine addiction.
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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.