ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Amphetamine Reverses Escalated Cocaine Intake via Restoration of Dopamine Transporter Conformation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Cocaine Use Disorder: Neuropathology and Exploratory Treatments.Molecular neurobiology · 2026Review
- Preclinical abuse potential testing using behavioral economics and drug self-administration demand-curve analysis: A strategy to improve resolution of drug stratification for regulatory control.Pharmacological reviews · 2026Review
- Differential effects of acute versus repeated chemogenetic activation of the mesocorticolimbic dopamine pathway on cocaine choice in male and female TH:Cre rats.ASPET discovery · 2026Article
- Intranasal cocaine self-administration in male mice.Nature communications · 2025Article
- Co-targeting the kappa opioid receptor and dopamine transporter reduces motivation to self-administer cocaine and partially reverses dopamine system dysregulation.Scientific reports · 2024Article
- Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's.The European journal of neuroscience · 2024Article
- Structural and functional perspectives on interactions between synthetic cathinones and monoamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine.Addiction neuroscience · 2023Article
- Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Systemic kappa opioid receptor antagonism accelerates reinforcement learning via augmentation of novelty processing in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Cocaine-regulated trafficking of dopamine transporters in cultured neurons revealed by a pH sensitive reporter.iScience · 2023Article
- Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.Addiction biology · 2023Review
- Overview of the structure and function of the dopamine transporter and its protein interactions.Frontiers in physiology · 2023Review
- Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction.Biological psychiatry · 2022Review
- D-amphetamine maintenance therapy reduces cocaine use in female rats.Psychopharmacology · 2022Review
- Phosphatidylinositol 4,5-bisphosphate (PIPCommunications biology · 2022Article
- Accurate and stable chroniciScience · 2022Article
- Functional characterization of the biogenic amine transporters on human macrophages.JCI insight · 2022Article
- Central Effects of the Designer Drug Mephedrone in Mice-Basic Studies.Brain sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Cocaine abuse disrupts dopamine system function, and reduces cocaine inhibition of the dopamine transporter (DAT), which results in tolerance. Although tolerance is a hallmark of cocaine addiction and a DSM-V criterion for substance abuse disorders, the molecular adaptations producing tolerance are unknown, and testing the impact of DAT changes on drug taking behaviors has proven difficult. In regard to treatment, amphetamine has shown efficacy in reducing cocaine intake; however, the mechanisms underlying these effects have not been explored. The goals of this study were twofold; we sought to (1) identify the molecular mechanisms by which cocaine exposure produces tolerance and (2) determine whether amphetamine-induced reductions in cocaine intake are connected to these mechanisms. Using cocaine self-administration and fast-scan cyclic voltammetry in male rats, we show that low-dose, continuous amphetamine treatment, during self-administration or abstinence, completely reversed cocaine tolerance. Amphetamine treatment also reversed escalated cocaine intake and decreased motivation to obtain cocaine as measured in a behavioral economics task, thereby linking tolerance to multiple facets of cocaine use. Finally, using fluorescence resonance energy transfer imaging, we found that cocaine tolerance is associated with the formation of DAT-DAT complexes, and that amphetamine disperses these complexes. In addition to extending our basic understanding of DATs and their role in cocaine reinforcement, we serendipitously identified a novel therapeutic target: DAT oligomer complexes. We show that dispersion of oligomers is concomitant with reduced cocaine intake, and propose that pharmacotherapeutics aimed at these complexes may have potential for cocaine addiction treatment.
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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.