Molecular pharmacology and physiology: Structure-function relationshipDiverse pre- and post-synaptic expression of m1–m4 muscarinic receptor proteins in neurons and afferents in the rat neostriatum
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Allosteric modulation of muscarinic receptors in alcohol and substance use disorders
2020, Advances in PharmacologyContribution of cholinergic interneurons to striatal pathophysiology in Parkinson's disease
2019, Neurochemistry InternationalCitation Excerpt :Several receptor localization studies in rodents report a predominant expression of M4 mAChRs within the striatum (45% of total striatal mAChRs) whereas M1 and M2 mAChRs are expressed at 30% and 20% of total striatal mAChRs, respectively (Chapman et al., 2011; Volpicelli and Levey, 2004; Waelbroeck et al., 1990; Yasuda et al., 1993). M3 mAChRs are clearly less abundant and M5 mAChRs are expressed at a very low level (Chapman et al., 2011; Hersch and Levey, 1995; Weiner et al., 1990; Yasuda et al., 1993). nAChRs constitute the second type of cholinergic receptors.
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2018, Neuroscience and Biobehavioral ReviewsCognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M<inf>4</inf> PAM VU0467154
2018, NeuropharmacologyCitation Excerpt :The current validation of the cognitive enhancing effects of the M4 PAM mechanism across 3 distinct cognitive assays that are in part dependent on different brain regions (Sacchetti et al., 2002; Zhang et al., 2001) after administration alone or in combination with a pharmacological challenge using both Pavlovian conditioning and operant approaches under conditions of a 10-day, once-daily dosing regimen provides further support for the clinical development of M4 PAMs to address one or more cognitive impairments observed in individuals with schizophrenia. Interestingly, M4 mAChRs are expressed throughout limbic and cortical brain regions known to be disrupted in individuals with schizophrenia, including the striatum, hippocampus, and cortex (Hersch and Levey, 1995; Levey et al., 1991; Rouse et al., 1999), and can function as autoreceptors in the striatum and midbrain (Tzavara et al., 2004; Zhang et al., 2002), as well as postsynaptic modulatory receptors in the striatum, neocortex, and hippocampus (Levey et al., 1991; Zang and Creese, 1997). Since efficacy was observed after 10-day, once daily administration of 10 mg/kg VU0467154 on enhancing the acquisition of memory in the cue-mediated conditioned freezing task and reversing both MK-801-induced impairments in the acquisition of a context-mediated conditioned freezing paradigm and induction of hyperactivity, these findings are consistent with the interpretation that selective M4 PAMs appear to provide a sufficient therapeutic index for potentially improving some of the positive and cognitive symptoms observed schizophrenia within the same dose range.