ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Long-term reduction of cocaine self-administration in rats treated with adenoviral vector-delivered cocaine hydrolase: evidence for enzymatic activity.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats.The Journal of pharmacology and experimental therapeutics · 2025Article
- In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase.Scientific reports · 2024Article
- Structure-Based Design and Discovery of a Long-Acting Cocaine Hydrolase Mutant with Improved Binding Affinity to Neonatal Fc Receptor for Treatment of Cocaine Abuse.The AAPS journal · 2020Article
- Environmental, genetic and epigenetic contributions to cocaine addiction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Review
- Treating Cocaine Addiction, Obesity, and Emotional Disorders by Viral Gene Transfer of Butyrylcholinesterase.Frontiers in pharmacology · 2018Review
- Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.Scientific reports · 2017Article
- Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.Chemico-biological interactions · 2016Article
- Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase.The Journal of pharmacology and experimental therapeutics · 2016Article
- Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice.The Journal of pharmacology and experimental therapeutics · 2016Article
- Reaction Pathway for Cocaine Hydrolase-Catalyzed Hydrolysis of (+)-Cocaine.Theoretical chemistry accounts · 2016Article
- Biologic Approaches to Treat Substance-Use Disorders.Trends in pharmacological sciences · 2015Review
- Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.Cellular and molecular neurobiology · 2015Article
- Kinetic characterization of a cocaine hydrolase engineered from mouse butyrylcholinesterase.The Biochemical journal · 2015Article
- The future potential for cocaine vaccines.Expert opinion on biological therapy · 2014Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
A new pharmacokinetic approach treating cocaine addiction involves rapidly metabolizing cocaine before it reaches brain reward centers using mutated human butyrylcholinesterase (BChE) or cocaine hydrolase (CocH). Recent work has shown that helper-dependent adenoviral (hdAD) vector-mediated plasma CocH reduced the locomotor-activating effects of cocaine and prevented reinstatement of cocaine-seeking behavior up to 6 months in rats. The present study investigated whether hdAD-CocH could decrease ongoing intravenous cocaine (0.4 mg/kg) self-administration. The hdAD-CocH vector was injected into self-administering rats, and after accumulation of plasma CocH, there was a dramatic reduction in cocaine infusions earned under a fixed ratio 1 schedule of reinforcement that lasted for the length of the study (>2 months). Pretreatment with the selective BChE and CocH inhibitor iso-OMPA (1.5 mg/kg) restored cocaine intake; therefore, the decline in self-administration was likely due to rapid CocH-mediated cocaine metabolism. Direct measurements of cocaine levels in plasma and brain samples taken after the conclusion of behavioral studies provided strong support for this conclusion. Further, rats injected with hdAD-CocH did not experience a deficit in operant responding for drug reinforcement and self-administered methamphetamine (0.05 mg/kg) at control levels. Overall, these outcomes suggest that viral gene transfer can yield plasma CocH levels that effectively diminish long-term cocaine intake and may have potential treatment implications for cocaine-dependent individuals seeking to become and remain abstinent.
Indexed as
Identifiers
What OpenQuestion holds
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.