Role of muscarinic M1 receptors in inhibitory avoidance and contextual fear conditioning

Soares, Juliana Carlota Kramer; Fornari, Raquel Vecchio; Oliveira, Maria Gabriela Menezes

doi:10.1016/j.nlm.2006.02.006

Cited by 41 publications

(33 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Systemic injections of nonselective muscarinic antagonists like scopolamine (Elrod and Buccafusco 1988) and M1 antagonists like pirenzipine have been shown to affect inhibitory avoidance in mice, when given before the training session (Ohnuki and Nomura 1996;Caulfield et al 1983;Worms et al 1989). Also, dicyclomine, the M1 selective antagonist used in this study, impairs the acquisition of inhibitory avoidance when given pre-training (Fornari et al 2000;Soares et al 2006) and post-training (Ghelardini et al 1998) suggesting the importance of M1 receptors in learning and memory. Also antisense knockdown of the M1 receptor in mice impaired inhibitory avoidance responses (Ghelardini et al 1999).…”

Section: Discussionmentioning

confidence: 59%

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

et al. 2011

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 59%

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The target for the enhanced cognition in response to this treatment was thought to be M 1 -muscarinic receptor signaling. This notion is based on the fact that the M 1 -muscarinic receptor is the most highly expressed muscarinic receptor subtype in the cortex and hippocampus (12) and that pharmacological studies point to this receptor subtype as being the primary effector of cholinergic-mediated cognition (6,24,25). However, recent studies using M 1 -muscarinic receptor knockout mice (1) together with studies using more selective pharmacological tools (9,10) have suggested that the M 1 -muscarinic receptor does not mediate hippocampal cognition directly.…”

Section: Discussionmentioning

confidence: 99%

The M ₃ -muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner

Poulin¹,

Butcher²,

McWilliams³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

141

View full text Add to dashboard Cite

Degeneration of the cholinergic system is considered to be the underlying pathology that results in the cognitive deficit in Alzheimer's disease. This pathology is thought to be linked to a loss of signaling through the cholinergic M 1 -muscarinic receptor subtype. However, recent studies have cast doubt on whether this is the primary receptor mediating cholinergic-hippocampal learning and memory. The current study offers an alternative mechanism involving the M 3 -muscarinic receptor that is expressed in numerous brain regions including the hippocampus. We demonstrate here that M 3 -muscarinic receptor knockout mice show a deficit in fear conditioning learning and memory. The mechanism used by the M 3 -muscarinic receptor in this process involves receptor phosphorylation because a knockin mouse strain expressing a phosphorylation-deficient receptor mutant also shows a deficit in fear conditioning. Consistent with a role for receptor phosphorylation, we demonstrate that the M 3 -muscarinic receptor is phosphorylated in the hippocampus following agonist treatment and following fear conditioning training. Importantly, the phosphorylation-deficient M 3 -muscarinic receptor was coupled normally to G q/11 -signaling but was uncoupled from phosphorylation-dependent processes such as receptor internalization and arrestin recruitment. It can, therefore, be concluded that M 3 -muscarinic receptor-dependent learning and memory depends, at least in part, on receptor phosphorylation/arrestin signaling. This study opens the potential for biased M 3 -muscarinic receptor ligands that direct phosphorylation/arrestin-dependent (non-G protein) signaling as being beneficial in cognitive disorders.A mong the multitude of physiological responses regulated by G protein-coupled receptors (GPCRs), one of the most intriguing is the ability of this superfamily of cell-surface receptors to regulate neurological and behavioral processes such as learning and memory (1-4). The members of the muscarinic acetylcholine receptor family are prominent among the GPCR subtypes associated with cognitive function because lesions in cholinergic innervations to the hippocampus and other brain areas are widely thought to underlie the cognitive deficit observed in Alzheimer's disease (5). Whereas the M 1 -muscarinic receptor subtype has been proposed to be the subtype associated with acetylcholine-mediated cognition (6, 7), recent gene-knockout experiments have cast doubt on the direct role of this receptor subtype in learning and memory (1,8). This has been reinforced by the discovery of a novel selective M 1 -muscarinic receptor antagonist that was effective in blocking M 1 -muscarinic receptor-mediated seizures in vivo but had no effect on hippocampal-based contextual fear conditioning (9). In addition, recent studies using an M 1 -muscarinic receptorpositive allosteric modulator, BQCA, have suggested that M 1 -muscarinic receptors can mediate learning and memory through an indirect mechanism by stimulating the prefrontal cortex (10). There is some con...

show abstract

“…Dicyclomine was administered 20 min prior to behavioral testing and was given at three doses (2.0, 4.0, and 8.0 mg/kg). Although higher doses of dicyclomine (16, 32, and 64 mg/kg; Soares et al 2006) have been used to Flower is the S+ when it is located in the left location, plane is the S+ when located in the middle location, and spider is the S+ when located in the right location. From Clelland et al (2009).…”

Section: Pharmacological Challengesmentioning

confidence: 99%

A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil

et al. 2010

View full text Add to dashboard Cite

The present study shows that mice can acquire the rodent PAL task and that the cholinergic system is important for PAL task performance. M(1) receptors in particular are likely implicated in normal performance of PAL. The finding that mouse PAL can detect both impairments and improvements indicates that this task could prove to be a highly valuable tool for a number of experimental aims including drug discovery.

show abstract

Role of muscarinic M1 receptors in inhibitory avoidance and contextual fear conditioning

Cited by 41 publications

References 43 publications

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

The M ₃ -muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner

A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil

Contact Info

Product

Resources

About

Role of muscarinic M1 receptors in inhibitory avoidance and contextual fear conditioning

Cited by 41 publications

References 43 publications

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome

The M 3 -muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner

A computer-automated touchscreen paired-associates learning (PAL) task for mice: impairments following administration of scopolamine or dicyclomine and improvements following donepezil

Contact Info

Product

Resources

About

The M ₃ -muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner