{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:19:39Z","timestamp":1791343179691,"version":"4.3.1"},"reference-count":71,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH86601"],"award-info":[{"award-number":["MH86601"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH87965"],"award-info":[{"award-number":["MH87965"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders.<\/jats:p>","DOI":"10.1021\/cn500128b","type":"journal-article","created":{"date-parts":[[2014,7,28]],"date-time":"2014-07-28T21:37:53Z","timestamp":1406583473000},"page":"920-942","source":"Crossref","is-referenced-by-count":156,"title":["Selective Activation of M4 Muscarinic Acetylcholine Receptors\nReverses MK-801-Induced Behavioral Impairments and Enhances Associative\nLearning in Rodents"],"prefix":"10.1021","volume":"5","author":[{"given":"Michael","family":"Bubser","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ditte","family":"Dencker","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital , , ,","place":["Copenhagen, Denmark, DK-2100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Gould","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grannan","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith J.","family":"Noetzel","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atin","family":"Lamsal","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Niswender","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Scott","family":"Daniels","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Poslusney","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Melancon","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Tarr","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Byers","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u0308rgen","family":"Wess","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , , ,","place":["Bethesda, Maryland, United States, 20814"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Duggan","sequence":"additional","affiliation":[{"name":"AstraZeneca , , 141 Portland Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dunlop","sequence":"additional","affiliation":[{"name":"AstraZeneca , , 141 Portland Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Wood","sequence":"additional","affiliation":[{"name":"AstraZeneca , , 141 Portland Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Brandon","sequence":"additional","affiliation":[{"name":"AstraZeneca , , 141 Portland Street , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Wood","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig W.","family":"Lindsley","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University , , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Jeffrey","family":"Conn","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie K.","family":"Jones","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt University Medical Center , , , ,","place":["Nashville, Tennessee, United States, 37232"]},{"name":"Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN) , , ,","place":["Nashville, Tennessee, United States, 37232"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,7,28]]},"reference":[{"key":"2026090316434515700_cit1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/mp.2013.136","article-title":"Imaging glutamate in schizophrenia:\nReview of findings\nand implications for drug discovery","volume":"19","author":"Poels","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"2026090316434515700_cit2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.brainresbull.2010.04.006","article-title":"N-methyl-d-aspartate\n(NMDA) receptor dysfunction or\ndysregulation: The final common pathway on the road to schizophrenia?","volume":"83","author":"Kantrowitz","year":"2010","journal-title":"Brain Res. Bull."},{"key":"2026090316434515700_cit3","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0074-7742(04)59019-0","article-title":"NMDA receptor function, neuroplasticity, and the pathophysiology\nof schizophrenia","volume":"59","author":"Coyle","year":"2004","journal-title":"Int. Rev. Neurobiol."},{"key":"2026090316434515700_cit4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1201\/9781420004335.ch4","article-title":"Involvement of the NMDA System\nin Learning and Memory","volume-title":"Animal Models of\nCognitive Impairment","author":"Rezvani","year":"2006"},{"key":"2026090316434515700_cit5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/978-3-642-23274-9_7","article-title":"Muscarinic receptor\npharmacology and circuitry for the modulation of cognition","author":"Bubser","year":"2012","journal-title":"Handb. Exp. Pharmacol."},{"key":"2026090316434515700_cit6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/npp.2011.199","article-title":"Muscarinic\nand nicotinic acetylcholine\nreceptor agonists and allosteric modulators for the treatment of schizophrenia","volume":"37","author":"Jones","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"2026090316434515700_cit7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1126\/science.3037705","article-title":"Identification of\na family of muscarinic acetylcholine receptor genes","volume":"237","author":"Bonner","year":"1987","journal-title":"Science"},{"key":"2026090316434515700_cit8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0896-6273(88)90190-0","article-title":"Cloning and expression\nof the human and rat m5 muscarinic acetylcholine receptor genes","volume":"1","author":"Bonner","year":"1988","journal-title":"Neuron"},{"key":"2026090316434515700_cit9","doi-asserted-by":"crossref","first-page":"10422","DOI":"10.1523\/JNEUROSCI.1850-08.2008","article-title":"Novel selective\nallosteric activator\nof the M1 muscarinic acetylcholine receptor regulates amyloid processing\nand produces antipsychotic-like activity in rats","volume":"28","author":"Jones","year":"2008","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit10","doi-asserted-by":"crossref","first-page":"14271","DOI":"10.1523\/JNEUROSCI.3930-09.2009","article-title":"A selective allosteric potentiator\nof the M1 muscarinic acetylcholine receptor increases activity of\nmedial prefrontal cortical neurons and restores impairments in reversal\nlearning","volume":"29","author":"Shirey","year":"2009","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit11","first-page":"1","article-title":"Direct and indirect modulation of\nthe N-methyl D-aspartate\nreceptor","volume":"1","author":"Marino","year":"2002","journal-title":"Curr. Drug Targets: CNS Neurol. Disord."},{"key":"2026090316434515700_cit12","doi-asserted-by":"crossref","first-page":"11465","DOI":"10.1073\/pnas.95.19.11465","article-title":"Activation\nof the genetically defined M1 muscarinic receptor potentiates N-methyl-D-asparate\n(NMDA) receptor currents in hippocampal pyramidal cells","volume":"95","author":"Marino","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026090316434515700_cit13","doi-asserted-by":"crossref","first-page":"13674","DOI":"10.1073\/pnas.1835612100","article-title":"N-Desmethylclozapine, an allosteric\nagonist at muscarinic 1 receptor, potentiate N-methyl-D-aspartate\nreceptor activity","volume":"100","author":"Sur","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U.\nS. A."},{"key":"2026090316434515700_cit14","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1523\/JNEUROSCI.0337-12.2012","article-title":"Novel allosteric agonists of M1 muscarinic acetylcholine\nreceptors induce brain region-specific responses that correspond with\nbehavioral effects in animal models","volume":"32","author":"Digby","year":"2012","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nn992","article-title":"Selective cognitive dysfunction in\nacetylcholine M1 muscarinic receptor mutant mice","volume":"6","author":"Anagnostaras","year":"2003","journal-title":"Nat. Neurosci."},{"key":"2026090316434515700_cit16","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1124\/jpet.108.140350","article-title":"Centrally\nactive allosteric potentiators of the M4 muscarinic acetylcholine\nreceptor reverse amphetamine-induced hyperlocomotor activity in rats","volume":"327","author":"Brady","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090316434515700_cit17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nchembio.2007.55","article-title":"An allosteric potentiator of M4 mAChR modulates hippocampal\nsynaptic transmission","volume":"4","author":"Shirey","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"2026090316434515700_cit18","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1038\/npp.2014.2","article-title":"Antipsychotic\ndrug-like effects of the selective M4 muscarinic acetylcholine receptor\npositive allosteric modulator VU0152100","volume":"39","author":"Byun","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"2026090316434515700_cit19","doi-asserted-by":"crossref","first-page":"10978","DOI":"10.1073\/pnas.0800567105","article-title":"Allosteric\nmodulation of the muscarinic\nM4 receptor as an approach to treating schizophrenia","volume":"105","author":"Chan","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026090316434515700_cit20","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/npp.2009.194","article-title":"Molecular\nmechanisms of action and in vivo validation of an M4 muscarinic acetylcholine\nreceptor allosteric modulator with potential antipsychotic properties","volume":"35","author":"Leach","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"2026090316434515700_cit21","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tips.2007.06.004","article-title":"Allosteric GPCR modulators: Taking\nadvantage of permissive receptor pharmacology","volume":"28","author":"Leach","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"2026090316434515700_cit22","doi-asserted-by":"crossref","first-page":"S40","DOI":"10.1007\/BF02245006","article-title":"Interaction\nof antipsychotic drugs with neurotransmitter receptor sites in vitro\nand in vivo in relation to pharmacological and clinical effects: Role\nof 5HT2 receptors","volume":"112","author":"Leysen","year":"1993","journal-title":"Psychopharmacology"},{"key":"2026090316434515700_cit23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0006-8993(93)91535-Z","article-title":"Occupancy of central\nneurotransmitter receptors by risperidone, clozapine and haloperidol,\nmeasured ex vivo by quantitative autoradiography","volume":"631","author":"Schotte","year":"1993","journal-title":"Brain Res."},{"key":"2026090316434515700_cit24","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S0022-3565(24)29291-0","article-title":"The muscarinic receptor agonist xanomeline\nhas an antipsychotic-like profile in the rat","volume":"299","author":"Stanhope","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090316434515700_cit25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-3-642-25758-2_10","article-title":"Glutamatergic\nsynaptic dysregulation in schizophrenia: therapeutic implications","author":"Coyle","year":"2012","journal-title":"Handb. Exp. Pharmacol."},{"key":"2026090316434515700_cit26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0028-3908(98)00163-4","article-title":"Differential actions\nof dizocilpine (MK-801) on the mesolimbic and mesocortical dopamine\nsystems: Role of neuronal activity","volume":"38","author":"Mathe","year":"1999","journal-title":"Neuropharmacology"},{"key":"2026090316434515700_cit27","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"Activation of glutamatergic\nneurotransmission by ketamine: A novel step in the pathway from NMDA\nreceptor blockade to dopaminergic and cognitive disruptions associated\nwith the prefrontal cortex","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit28","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1523\/JNEUROSCI.18-14-05545.1998","article-title":"Corticolimbic\ndopamine neurotransmission is temporally\ndissociated from the cognitive and locomotor effects of phencyclidine","volume":"18","author":"Adams","year":"1998","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit29","doi-asserted-by":"crossref","first-page":"8467","DOI":"10.1073\/pnas.0308455101","article-title":"NMDA receptor hypofunction produces\nconcomitant firing rate potentiation and burst activity reduction\nin the prefrontal cortex","volume":"101","author":"Jackson","year":"2004","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"key":"2026090316434515700_cit30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/0006-8993(75)90233-4","article-title":"Amphetamine and apomorphine responses\nin the rat following 6-OHDA lesions of the nucleus accumbens septi\nand corpus striatum","volume":"94","author":"Kelly","year":"1975","journal-title":"Brain Res."},{"key":"2026090316434515700_cit31","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/0028-3908(83)90051-5","article-title":"Effect\nof injections of 6-OHDA into\neither nucleus accumbens septi or frontal cortex on spontaneous and\ndrug-induced activity","volume":"22","author":"Joyce","year":"1983","journal-title":"Neuropharmacology"},{"key":"2026090316434515700_cit32","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0006-8993(87)91416-8","article-title":"A direct comparison\nof amphetamine-induced behaviours and regional brain dopamine release\nin the rat using intracerebral dialysis","volume":"401","author":"Sharp","year":"1987","journal-title":"Brain\nRes."},{"key":"2026090316434515700_cit33","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0091-3057(85)90025-5","article-title":"A rapid and\nsimple behavioural screening method for\nsimultaneous assessment of limbic and striatal blocking effects of\nneuroleptic drugs","volume":"23","author":"Ljungberg","year":"1985","journal-title":"Pharmacol., Biochem. Behav."},{"key":"2026090316434515700_cit34","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0014-2999(92)90288-F","article-title":"Differential behavioural\nand neurochemical effects of competitive and non-competitive NMDA\nreceptor antagonists in rats","volume":"229","author":"Bubser","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"2026090316434515700_cit35","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF01244704","article-title":"A comparison\nbetween the non-competitive\nNMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist\nD-CPPene with regard to dopamine turnover and locomotor-stimulatory\nproperties in mice","volume":"85","author":"Svensson","year":"1991","journal-title":"J. Neural Transm.: Gen.\nSect."},{"key":"2026090316434515700_cit36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0014-2999(91)90381-Y","article-title":"Effect of the NMDA\nreceptor antagonist, MK-801, on locomotor activity and on the metabolism\nof dopamine in various brain areas of mice","volume":"195","author":"Liljequist","year":"1991","journal-title":"Eur. J. Pharmacol."},{"key":"2026090316434515700_cit37","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.neuropharm.2011.08.023","article-title":"Intact attentional processing but abnormal responding\nin M1 muscarinic receptor-deficient mice using an automated touchscreen\nmethod","volume":"61","author":"Bartko","year":"2011","journal-title":"Neuropharmacology"},{"key":"2026090316434515700_cit38","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1101\/lm.777308","article-title":"Impaired discrimination learning\nin mice lacking the\nNMDA receptor NR2A subunit","volume":"15","author":"Brigman","year":"2008","journal-title":"Learn. Mem."},{"key":"2026090316434515700_cit39","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1101\/lm.987808","article-title":"The touchscreen\ncognitive testing method for rodents:\nHow to get the best out of your rat","volume":"15","author":"Bussey","year":"2008","journal-title":"Learn.\nMem."},{"key":"2026090316434515700_cit40","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1038\/nprot.2013.122","article-title":"The touchscreen operant platform\nfor testing learning and memory in rats and mice","volume":"8","author":"Horner","year":"2013","journal-title":"Nat. Protoc."},{"key":"2026090316434515700_cit41","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00213-011-2225-4","article-title":"Increased\ncocaine self-administration in M4 muscarinic acetylcholine receptor\nknockout mice","volume":"216","author":"Schmidt","year":"2011","journal-title":"Psychopharmacology"},{"key":"2026090316434515700_cit42","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0166-4328(01)00256-X","article-title":"The ventral\nhippocampus and fear\nconditioning in rats: Different anterograde amnesias of fear after\ninfusion of N-methyl-D-aspartate or its noncompetitive antagonist\nMK-801 into the ventral hippocampus","volume":"126","author":"Zhang","year":"2001","journal-title":"Behav.\nBrain Res."},{"key":"2026090316434515700_cit43","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/00008877-200207000-00005","article-title":"MK-801\ndisrupts acquisition of contextual\nfear conditioning but enhances memory consolidation of cued fear conditioning","volume":"13","author":"Gould","year":"2002","journal-title":"Behav. Pharmacol."},{"key":"2026090316434515700_cit44","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1001\/archneur.1997.00550160091022","article-title":"Effects of xanomeline, a selective muscarinic receptor\nagonist, on cognitive function and behavioral symptoms in Alzheimer\ndisease","volume":"54","author":"Bodick","year":"1997","journal-title":"Arch. Neurol."},{"key":"2026090316434515700_cit45","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1016\/S0024-3205(01)01059-1","article-title":"Elucidating the role of muscarinic\nreceptors in psychosis","volume":"68","author":"Felder","year":"2001","journal-title":"Life Sci."},{"key":"2026090316434515700_cit46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/BF00401402","article-title":"Comprehensive\nobservational assessment: Ia. A systematic, quantitative procedure\nfor assessing the behavioral and physiologic state of the mouse","volume":"13","author":"Irwin","year":"1968","journal-title":"Psychopharmacologia"},{"key":"2026090316434515700_cit47","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s002130050942","article-title":"L-701,324,\na selective antagonist at the glycine site of the NMDA receptor, counteracts\nhaloperidol-induced muscle rigidity in rats","volume":"143","author":"Konieczny","year":"1999","journal-title":"Psychopharmacology"},{"key":"2026090316434515700_cit48","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1080\/00207450902984002","article-title":"Rotarod impairment: Catalepsy-like\nscreening test for antipsychotic side effects","volume":"119","author":"Kirschbaum","year":"2009","journal-title":"Int. J. Neurosci."},{"key":"2026090316434515700_cit49","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S0006-3223(00)01017-9","article-title":"The muscarinic agonist xanomeline increases monoamine\nrelease and immediate early gene expression in the rat prefrontal\ncortex","volume":"49","author":"Perry","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"2026090316434515700_cit50","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0022-3565(24)34979-1","article-title":"Muscarinic receptor agonists, like dopamine receptor\nantagonist antipsychotics, inhibit conditioned avoidance response\nin rats","volume":"290","author":"Shannon","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026090316434515700_cit51","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0920-9964(99)00138-3","article-title":"Xanomeline, an M(1)\/M(4) preferring\nmuscarinic cholinergic receptor agonist, produces antipsychotic-like\nactivity in rats and mice","volume":"42","author":"Shannon","year":"2000","journal-title":"Schizophr. Res."},{"key":"2026090316434515700_cit52","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0304-3940(90)90823-R","article-title":"Non-competitive N-methyl-D-aspartate\nantagonists are potent activators\nof ventral tegmental A10 dopamine neurons","volume":"119","author":"French","year":"1990","journal-title":"Neurosci.\nLett."},{"key":"2026090316434515700_cit53","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0014-2999(94)90404-9","article-title":"Locomotor activation induced by MK-801\nin the rat: postsynaptic interactions with dopamine receptors in the\nventral striatum","volume":"251","author":"Ouagazzal","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"2026090316434515700_cit54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0166-4328(95)80004-2","article-title":"Effects of D1 and\nD2 dopamine receptor antagonists\nand catecholamine depleting agents on the locomotor stimulation induced\nby dizocilpine in mice","volume":"70","author":"Lapin","year":"1995","journal-title":"Behav. Brain Res."},{"key":"2026090316434515700_cit55","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1523\/JNEUROSCI.3843-09.2010","article-title":"A subpopulation of\nneuronal M4 muscarinic acetylcholine receptors\nplays a critical role in modulating dopamine-dependent behaviors","volume":"30","author":"Jeon","year":"2010","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit56","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1523\/JNEUROSCI.0370-11.2011","article-title":"Involvement of a subpopulation of neuronal M4 muscarinic\nacetylcholine receptors in the antipsychotic-like effects of the M1\/M4\npreferring muscarinic receptor agonist xanomeline","volume":"31","author":"Dencker","year":"2011","journal-title":"J. Neurosci."},{"key":"2026090316434515700_cit57","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1021\/cn500003z","article-title":"M4 mAChR-Mediated Modulation of Glutamatergic Transmission at Corticostriatal\nSynapses","volume":"5","author":"Pancani","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"2026090316434515700_cit58","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cell.2011.10.009","article-title":"Molecular mechanisms\nof fear learning and memory","volume":"147","author":"Johansen","year":"2011","journal-title":"Cell"},{"key":"2026090316434515700_cit59","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/72945","article-title":"Enrichment induces\nstructural changes and recovery\nfrom nonspatial memory deficits in CA1 NMDAR1-knockout mice","volume":"3","author":"Rampon","year":"2000","journal-title":"Nat. Neurosci."},{"key":"2026090316434515700_cit60","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1126\/science.290.5494.1170","article-title":"NMDA receptor-dependent\nsynaptic reinforcement as a crucial process for memory consolidation","volume":"290","author":"Shimizu","year":"2000","journal-title":"Science"},{"key":"2026090316434515700_cit61","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.nlm.2011.01.008","article-title":"Behavioral\nanalysis of NR2C knockout mouse reveals deficit in acquisition of\nconditioned fear and working memory","volume":"95","author":"Hillman","year":"2011","journal-title":"Neurobiol.\nLearn. Mem."},{"key":"2026090316434515700_cit62","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1756-6606-5-10","article-title":"M4 muscarinic receptor knockout mice\ndisplay abnormal social behavior and decreased prepulse inhibition","volume":"5","author":"Koshimizu","year":"2012","journal-title":"Mol. Brain"},{"key":"2026090316434515700_cit63","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00221-002-1165-y","article-title":"Differential\ncontribution of some cortical sites to the formation of memory traces\nsupporting fear conditioning","volume":"146","author":"Sacchetti","year":"2002","journal-title":"Exp. Brain Res."},{"key":"2026090316434515700_cit64","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000357682","article-title":"Effects of selective activation of\nm1 and m4 muscarinic\nreceptors on object recognition memory performance in rats","volume":"93","author":"Galloway","year":"2014","journal-title":"Pharmacology"},{"key":"2026090316434515700_cit65","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1176\/ajp.2007.164.7.1061","article-title":"Effects of olanzapine, quetiapine,\nand risperidone on neurocognitive function in early psychosis: a randomized,\ndouble-blind 52-week comparison","volume":"164","author":"Keefe","year":"2007","journal-title":"Am. J. Psychiatry"},{"key":"2026090316434515700_cit66","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1176\/ps.2008.59.5.500","article-title":"What CATIE\nfound: Results from the schizophrenia trial","volume":"59","author":"Swartz","year":"2008","journal-title":"Psychiatr. Serv."},{"key":"2026090316434515700_cit67","unstructured":"Rubio, A., Hilliard, D. W. (2006) Thienopyridines as allosteric potentiators of the m4 muscarinic receptor. Int. Patent WO 2006047124 A1."},{"key":"2026090316434515700_cit68","doi-asserted-by":"crossref","first-page":"5208","DOI":"10.1021\/jm400439t","article-title":"Discovery of (R)-(2-fluoro-4-((\u22124-methoxyphenyl)ethynyl)phenyl)\n(3-hydroxypiperidin-1-yl)methanone (ML337), an mGlu3 selective and\nCNS penetrant negative allosteric modulator (NAM)","volume":"56","author":"Wenthur","year":"2013","journal-title":"J. Med. Chem."},{"key":"2026090316434515700_cit69","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.neures.2006.02.005","article-title":"5-HT(2C) receptor\nRNA editing in the amygdala of C57BL\/6J, DBA\/2J, and BALB\/cJ mice","volume":"55","author":"Hackler","year":"2006","journal-title":"Neurosci. Res"},{"key":"2026090316434515700_cit70","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1021\/cn900003h","article-title":"Discovery and characterization of\nnovel subtype-selective allosteric agonists for the investigation\nof M1 receptor function in the central nervous system","volume":"1","author":"Lebois","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"2026090316434515700_cit71","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbr.2011.01.052","article-title":"Effects of\nthe cognition impairer MK-801 on learning and memory in mice and rats","volume":"220","author":"van der Staay","year":"2011","journal-title":"Behav. Brain Res."}],"container-title":["ACS Chemical Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cn500128b","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acncdm\/article-pdf\/5\/10\/920\/8042488\/cn500128b.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acncdm\/article-pdf\/5\/10\/920\/8042488\/cn500128b.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:44:00Z","timestamp":1788468240000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acncdm\/article\/5\/10\/920\/784052\/Selective-Activation-of-M4-Muscarinic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,28]]},"references-count":71,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,7,28]]},"published-print":{"date-parts":[[2014,10,15]]}},"URL":"https:\/\/doi.org\/10.1021\/cn500128b","relation":{},"ISSN":["1948-7193"],"issn-type":[{"value":"1948-7193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,28]]}}}