The effect of chronic atropine administration on mouse motility and on ACh levels in the central nervous system

Molinengo, L; Fundarò, A; Orsetti, Marco

doi:10.1016/0091-3057(89)90085-3

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…However, M 1 R Ϫ/Ϫ mice displayed a pronounced increase in locomotor activity that was consistently observed in all tests that included locomotor activity measurements. Consistent with this observation, it is well known that centrally active muscarinic agonists or antagonists can cause pronounced changes in locomotor activity levels (Molinengo et al, 1989;Shannon and Peters, 1990;Ukai et al, 1994). A hyperactivity phenotype was not seen with mutant mouse strains lacking M 2 (Gomeza et al, 1999a) or M 3 muscarinic receptors (Yamada et al, 2001).…”

Section: Hyperactivity Of M 1 R ؊/؊ Micesupporting

confidence: 61%

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor

et al. 2001

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Members of the muscarinic acetylcholine receptor family are thought to play key roles in the regulation of a large number of important functions of the CNS. However, the precise roles of the individual muscarinic receptor subtypes in modulating these processes are not well understood at present, primarily because of the lack of ligands with sufficient receptor subtype selectivity. To investigate the behavioral significance of the M 1 muscarinic receptor (M 1 R), which is abundantly expressed in the forebrain, we subjected M 1 receptor-deficient mice Ϫ/Ϫ mice showed slight performance deficits in auditory-cued fear conditioning and in an eight-arm radial maze, most likely because of the hyperactivity phenotype displayed by the M 1 R Ϫ/Ϫ mice. Our results indicate that M 1 muscarinic receptors play an important role in the regulation of locomotor activity but appear to be less critical for cognitive processes, as generally assumed.

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Section: Hyperactivity Of M 1 R ؊/؊ Micesupporting

confidence: 61%

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor

et al. 2001

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“…Furthermore, we observed substantial effects even with a very low dose of atropine (0.2 mg/kg twice daily for 7 days; Fig. 1 C-F), which was the same or less than the doses used in most studies of muscarinic signaling (Molinengo et al, 1989; Kociolek et al, 2006). Lastly, when we applied atropine at the lowest dose (0.2mg/kg once-daily for only 5 days; n=6 mice), we found milder defects that were confined to the synaptic area, and both preterminal axons and myelinating Schwann cells appeared completely normal (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 69%

Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses

Wright¹,

Potluri²,

Wang³

et al. 2009

J. Neurosci.

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Muscarinic acetylcholine receptors (mAChRs) modulate synaptic function, but whether they influence synaptic structure remains unknown. At neuromuscular junctions (NMJs), mAChRs have been implicated in compensatory sprouting of axon terminals in paralyzed or denervated muscles. Here we used pharmacological and genetic inhibition and localization studies of mAChR subtypes at mouse NMJs to demonstrate their roles in synaptic stability and growth but not in compensatory sprouting. M 2 mAChRs were present solely in motor neurons, whereas M 1 , M 3 , and M 5 mAChRs were associated with Schwann cells and/or muscle fibers. Blockade of all five mAChR subtypes with atropine evoked pronounced effects, including terminal sprouting, terminal withdrawal, and muscle fiber atrophy. In contrast, methoctramine, an M 2/4 -preferring antagonist, induced terminal sprouting and terminal withdrawal, but no muscle fiber atrophy. Consistent with this observation, M 2Ϫ/Ϫ but no other mAChR mutant mice exhibited spontaneous sprouting accompanied by extensive loss of parental terminal arbors. Terminal sprouting, however, seemed not to be the causative defect because partial loss of terminal branches was common even in the M 2 Ϫ/Ϫ NMJs without sprouting. Moreover, compensatory sprouting after paralysis or partial denervation was normal in mice deficient in M 2 or other mAChR subtypes. We also found that many NMJs of M 5 Ϫ/Ϫ mice were exceptionally small and reduced in proportion to the size of parental muscle fibers. These findings show that axon terminals are unstable without M 2 and that muscle fiber growth is defective without M 5 . Subtype-specific muscarinic signaling provides a novel means for coordinating activity-dependent development and maintenance of the tripartite synapse.

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“…Injection of muscarinic antagonists in distinct brain regions cause pronounced augmentation in locomotor activity levels [32], [33], [35] and a hyperactivity phenotype was observed in mouse strains lacking M1 and M4 muscarinic receptors [30], [31], [52] as well as mouse strains null for the nicotinic β2 receptor [29], [36], [37]. Paradoxically, systemic injections of nicotinic agonists can cause an increase in locomotor activity [53]–[56].…”

Section: Discussionmentioning

confidence: 99%

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

et al. 2011

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Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to “turn down” neuronal circuits controlling locomotion.

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The effect of chronic atropine administration on mouse motility and on ACh levels in the central nervous system

Cited by 12 publications

References 5 publications

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor

Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

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The effect of chronic atropine administration on mouse motility and on ACh levels in the central nervous system

Cited by 12 publications

References 5 publications

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M1Muscarinic Acetylcholine Receptor

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M1Muscarinic Acetylcholine Receptor

Distinct Muscarinic Acetylcholine Receptor Subtypes Contribute to Stability and Growth, But Not Compensatory Plasticity, of Neuromuscular Synapses

Novel Strains of Mice Deficient for the Vesicular Acetylcholine Transporter: Insights on Transcriptional Regulation and Control of Locomotor Behavior

Contact Info

Product

Resources

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Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor

Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M₁Muscarinic Acetylcholine Receptor