ArticlePsychopharmacology2012
Contribution of both M1 and M4 receptors to muscarinic agonist-mediated attenuation of the cocaine discriminative stimulus in mice.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Selective modulation of murine intestinal MAmerican journal of physiology. Cell physiology · 2026Article
- The Novel Functions of M4 Muscarinic Receptors.Physiological research · 2025Review
- Xanomeline treatment attenuates cocaine self-administration in rats and nonhuman primates.Neuropharmacology · 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
- Effects of acute and repeated administration of the selective MAddiction biology · 2022Article
- MPharmacology research & perspectives · 2022Article
- CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors.Neurobiology of disease · 2021Article
- Effects of muscarinic MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Targeting Muscarinic Acetylcholine Receptors for the Treatment of Psychiatric and Neurological Disorders.Trends in pharmacological sciences · 2019Review
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Physiological roles of CNS muscarinic receptors gained from knockout mice.Neuropharmacology · 2018Review
- Effects of muscarinic MPsychopharmacology · 2018Article
- Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.Drug and alcohol dependence · 2017Article
- Muscarinic receptor MDrug and alcohol dependence · 2017Article
- Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor MBehavioural brain research · 2017Article
- Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.Journal of computational chemistry · 2017Article
- Prefrontal Cortex-Mediated Impairments in a Genetic Model of NMDA Receptor Hypofunction Are Reversed by the Novel MACS chemical neuroscience · 2016Article
- 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
- Cholinergic interneurons in the dorsal and ventral striatum: anatomical and functional considerations in normal and diseased conditions.Annals of the New York Academy of Sciences · 2015Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleWe previously showed that muscarinic agonists with M(1) and/or M(4) receptor affinities attenuated cocaine discrimination and self-administration in wild-type mice but not in M(1)/M(4) double-knockout mice.
objectiveThis study aims to elucidate the respective contributions of M(1) and M(4) receptors to this effect.
methodsKnockout mice lacking either the M(1) subtype (M (1) (-/-) ) or the M(4) subtype (M (4) (-/-) ) and wild-type mice were trained to discriminate 10 mg/kg cocaine from saline. Muscarinic ligands were tested for modulation of cocaine discrimination: xanomeline (M(1)/M(4)-preferring agonist), VU0357017 (M(1)-selective partial agonist), 77-LH-28-1 (M(1) agonist), and BQCA (M(1)-selective positive allosteric modulator).
resultsXanomeline produced rightward shifts in the cocaine dose-effect curve in all three genotypes, but most robustly in wild-type mice. VU0357017 produced rightward shifts in the cocaine dose-effect curve in wild-type and M (4) (-/-) mice, but not in M (1) (-/-) mice. Response rates were suppressed by xanomeline in wild-type and M (1) (-/-) but not in M (4) (-/-) mice and were unaltered by VU0357017. 77-LH-28-1 and BQCA also showed evidence of attenuating cocaine's discriminative stimulus, but at doses that suppressed responding or had other undesirable effects. Intriguingly, both VU0357017 and 77-LH-28-1 exhibited U-shaped dose-effect functions in attenuating cocaine discrimination. None of the drugs substituted for the cocaine stimulus.
conclusionsAttenuation of the cocaine stimulus by VU0357017 depended upon M(1) receptors, and full effects of xanomeline depended upon both M(1) and M(4) receptors. Therefore M(1)-selective agonists and mixed M(1)/M(4) agonists may be promising leads for developing medications that block cocaine's effects.
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