ReviewBehavioural brain research2016
A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders.
Review in Behavioural brain research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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
20 citing papers in PubMed, 38 citations in OpenAlex.
- Effects of Biperiden (Cholinergic Muscarinic m1/m4 Receptor Antagonist) on Craving Nicotine: A Proof-Of-Concept Clinical Study.European addiction research · 2025Trial
- Randomized placebo-controlled trial of galantamine in individuals with cocaine use disorder.Journal of substance abuse treatment · 2019Trial
- Double-Blind Placebo-Controlled Trial of Galantamine for Methadone-Maintained Individuals With Cocaine Use Disorder: Secondary Analysis of Effects on Illicit Opioid Use.The American journal on addictions · 2019Trial
- Galantamine and Computerized Cognitive Behavioral Therapy for Cocaine Dependence: A Randomized Clinical Trial.The Journal of clinical psychiatryTrial
- Article
- Distinct cholinergic circuits underlie discrete effects of reward on attention.Frontiers in molecular neuroscience · 2024Review
- Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward.Frontiers in molecular neuroscience · 2024Article
- Selective Modulation of Hippocampal Theta Oscillations in Response to Morphine versus Natural Reward.Brain sciences · 2023Article
- M3 Receptor Pathway Stimulates Rapid Transcription of the CB1 Receptor Activation through Calcium Signalling and the CNR1 Gene Promoter.International journal of molecular sciences · 2023Article
- Multiple cholinesterase inhibitors have antidepressant-like properties in the mouse forced swim test.Behavioural brain research · 2021Article
- Norepinephrine May Oppose Other Neuromodulators to Impact Alzheimer's Disease.International journal of molecular sciences · 2021Article
- The cholinesterase inhibitor donepezil has antidepressant-like properties in the mouse forced swim test.Translational psychiatry · 2020Article
- Repurposing Cholinesterase Inhibitors as Antidepressants? Dose and Stress-Sensitivity May Be Critical to Opening Possibilities.Frontiers in behavioral neuroscience · 2020Review
- Profound alteration in reward processing due to a human polymorphism in CHRNA5: a role in alcohol dependence and feeding behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- The muscarinic agonist pilocarpine modifies cocaine-reinforced and food-reinforced responding in rats: comparison with the cholinesterase inhibitor tacrine.Behavioural pharmacology · 2019Article
- Striatal Cholinergic Interneurons Are a Novel Target of Corticotropin Releasing Factor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Letter to the Editor: A Novel Therapeutic for Opioid Use Disorder Targeting the Cholinergic System.The American journal on addictions · 2019Article
- Muscarinic M4 Receptors on Cholinergic and Dopamine D1 Receptor-Expressing Neurons Have Opposing Functionality for Positive Reinforcement and Influence Impulsivity.Frontiers in molecular neuroscience · 2018Article
- Extracellular dopamine, acetylcholine, and activation of dopamine D1 and D2 receptors after selective breeding for cocaine self-administration in rats.Psychopharmacology · 2017Article
- Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The cholinergic system plays important roles in both learning and addiction. Medications that modify cholinergic tone can have pronounced effects on behaviors reinforced by natural and drug reinforcers. Importantly, enhancing the action of acetylcholine (ACh) in the nucleus accumbens and ventral tegmental area (VTA) dopamine system can either augment or diminish these behaviors. A threshold model is presented that can explain these seemingly contradictory results. Relatively low levels of ACh rise above a lower threshold, facilitating behaviors supported by drugs or natural reinforcers. Further increases in cholinergic tone that rise above a second upper threshold oppose the same behaviors. Accordingly, cholinesterase inhibitors, or agonists for nicotinic or muscarinic receptors, each have the potential to produce biphasic effects on reward behaviors. Pretreatment with either nicotinic or muscarinic antagonists can block drug- or food- reinforced behavior by maintaining cholinergic tone below its lower threshold. Potential threshold mediators include desensitization of nicotinic receptors and biphasic effects of ACh on the firing of medium spiny neurons. Nicotinic receptors with high- and low- affinity appear to play greater roles in reward enhancement and inhibition, respectively. Cholinergic inhibition of natural and drug rewards may serve as mediators of previously described opponent processes. Future studies should evaluate cholinergic agents across a broader range of doses, and include a variety of reinforced behaviors.
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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.