ArticlePsychopharmacology2014
Acute and chronic effects of the M1/M4-preferring muscarinic agonist xanomeline on cocaine vs. food choice in rats.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- The effects of acute and repeated M1 agonist VU0364572 administration on cocaine-vs-food choice in male and female Sprague-Dawley rats.Drug and alcohol dependence · 2026Article
- Effects of nonpharmacological manipulations and repeated xanomeline treatment on methamphetamine-vs-food choice in Sprague Dawley and Long Evans rats.Drug and alcohol dependence · 2026Article
- Assessing behavioral reallocation after acute environmental manipulations using an asymmetric cocaine versus sucrose choice task in male and female rats.Psychopharmacology · 2026Article
- Xanomeline treatment attenuates cocaine self-administration in rats and nonhuman primates.Neuropharmacology · 2025Article
- Assessing behavioral reallocation after acute environmental manipulations using an asymmetric cocaine versus sucrose choice task in male and female rats.Research square · 2025Article
- Mechanistic and translational insights from preclinical cocaine choice procedures on the economic substitutability of cocaine and nondrug reinforcers.Neuroscience and biobehavioral reviews · 2025Review
- [Pharmacological reports : PR · 2025Article
- Co-stimulation of muscarinic M1 and M4 acetylcholine receptors prevents later cocaine reinforcement in male and female mice, but not place-conditioning.Progress in neuro-psychopharmacology & biological psychiatry · 2024Article
- Role of Efficacy as a Determinant of Locomotor Activation by Mu Opioid Receptor Ligands in Female and Male Mice.The Journal of pharmacology and experimental therapeutics · 2022Article
- Effects of acute and repeated administration of the selective MAddiction biology · 2022Article
- MPharmacology research & perspectives · 2022Article
- Effects of muscarinic MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Effects of muscarinic MPsychopharmacology · 2018Article
- Heroin and saccharin demand and preference in rats.Drug and alcohol dependence · 2017Article
- Muscarinic receptor MDrug and alcohol dependence · 2017Article
- Effects of Acute and Chronic Treatments with Dopamine DThe Journal of pharmacology and experimental therapeutics · 2017Article
- Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor MBehavioural brain research · 2017Article
- Insights from Preclinical Choice Models on Treating Drug Addiction.Trends in pharmacological sciences · 2017Review
- A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders.Behavioural brain research · 2016Review
- Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice.European journal of pharmacology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleWe previously showed that the M1/M4-preferring muscarinic agonist xanomeline can acutely attenuate or eliminate cocaine self-administration in mice.
objectiveMedications used to treat addictions will arguably be administered in (sub)chronic or repeated regimens. Tests of acute effects often fail to predict chronic effects, highlighting the need for chronic testing of candidate medications.
methodsRats were trained to lever press under a concurrent FR5 FR5 schedule of intravenous cocaine and food reinforcement. Once baseline behavior stabilized, the effects of 7 days once-daily injections of xanomeline were evaluated.
resultsXanomeline pretreatment dose-dependently (1.8-10 mg/kg/day) shifted the dose-effect curve for cocaine rightward (up to 5.6-fold increase in A 50), with reallocation of behavior to the food-reinforced lever. There was no indication of tolerance, rather effects grew over days. The suppression of cocaine choice appeared surmountable at high cocaine doses, and xanomeline treatment did not significantly decrease total-session cocaine or food intake.
conclusionsIn terms of xanomeline's potential for promoting abstinence from cocaine in humans, the findings were mixed. Xanomeline did produce reallocation of behavior from cocaine to food with a robust increase in food reinforcers earned at some cocaine/xanomeline dose combinations. However, effects appeared surmountable, and food-maintained behavior was also decreased at some xanomeline/cocaine dose combinations, suggesting clinical usefulness may be limited. These data nevertheless support the notion that chronic muscarinic receptor stimulation can reduce cocaine self-administration. Future studies should show whether ligands with higher selectivity for M1 or M1/M4 subtypes would be less limited by undesired effects and can achieve higher efficacy.
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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.