ArticleBehavioral neuroscience2015
Low expression of D2R and Wntless correlates with high motivation for heroin.
Article in Behavioral neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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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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.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Higher levels of D2R and D3R in the frontal-striatal regions are associated with reduced perseverative reward seeking after opioid abstinence.Frontiers in behavioral neuroscience · 2025Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin.Psychiatry investigation · 2022Article
- Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Dopamine Receptor DRD2 Gene rs1076560, Personality Traits and Anxiety in the Polysubstance Use Disorder.Brain sciences · 2020Article
- Associations Between Adolescent Chronic Pain and Prescription Opioid Misuse in Adulthood.The journal of pain · 2019Article
- Cocaine Self-administration Alters Transcriptome-wide Responses in the Brain's Reward Circuitry.Biological psychiatry · 2018Article
- Identifying novel members of the Wntless interactome through genetic and candidate gene approaches.Brain research bulletin · 2018Article
- Preweaning iron deficiency increases non-contingent responding during cocaine self-administration in rats.Physiology & behavior · 2016Article
- Early avoidance of a heroin-paired taste-cue and subsequent addiction-like behavior in rats.Brain research bulletin · 2016Article
- Greater avoidance of a heroin-paired taste cue is associated with greater escalation of heroin self-administration in rats.Behavioral neuroscience · 2015Article
- Hypothesizing Balancing Endorphinergic and Glutaminergic Systems to Treat and Prevent Relapse to Reward Deficiency Behaviors: Coupling D-Phenylalanine and N-Acetyl-L-Cysteine (NAC) as a Novel Therapeutic Modality.Clinical medical reviews and case reportsArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.
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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.