The role of the cholinergic system in the signal attenuation rat model of obsessive-compulsive disorder

Yankelevitch-Yahav, Roni; Joel, Daphna

doi:10.1007/s00213-013-3134-5

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…Evidence exists for cholinergic involvement in OCD (Lucey et al, 1993; Yankelevitch-Yahav and Joel, 2013). Some studies have indicated exacerbation of OCD symptoms induced by nicotine (Abramovitch et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Mitra

Mucha

Khatri

et al. 2017

Front. Behav. Neurosci.

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Nicotinic α4β2 receptors are the most abundant subtypes of nicotinic acetylcholine receptors (nAChRs) expressed in brain regions implicated in obsessive compulsive disorder (OCD). These receptors are known to modify normal and addictive behaviors by modulating neuronal excitability. Desformylflustrabromine (dFBr) is a novel, positive allosteric modulator (PAM) of high acetylcholine sensitivity (HS) and low acetylcholine sensitivity (LS) α4β2 nAChRs. The present study tested the hypothesis that positive allosteric modulation of α4β2 receptors by dFBr will attenuate compulsive-like behavior in a non-induced compulsive-like mouse model. Male mice (Mus musculus) selected for compulsive-like nesting behavior (NB; 48 animals; 12 per group) received acute (once) and chronic (every day for 32 days) subcutaneous injection of dFBr at 2, 4 and 6 mg/kg doses. Saline was used as a control (0 mg/kg). Compulsive-like NB was assessed after 1, 2, 3, 4, 5 and 24 h, while compulsive-like marble burying (MB) and anxiety-like open field (OF) behaviors were performed 2 h after dFBr administration. In the acute administration protocol, dFBr dose dependently attenuated NB and MB. Rapid effects (1–2 h after drug administration) of dFBr on MB and NB were observed for the chronic administration which was in congruence with the acute study. Chronic administration also revealed sustained suppression of NB by dFBr following 5 weeks of treatment. In both the acute and chronic regimen dFBr did not modulate OF behaviors. This research demonstrates the novel role of positive allosteric modulation of α4β2 nicotinic receptors by dFBr as a translational potential for OCD.

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Section: Discussionmentioning

confidence: 99%

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Mitra

Mucha

Khatri

et al. 2017

Front. Behav. Neurosci.

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“…An animal model showed that cholinergic interneurons’ activity in NAC were associated with adaptive cue-motivated behavior, present in many psychiatric conditions [ 39 ]. Acetylcholine seems to not interfere with signal attenuation in the cholinergic system of compulsive behavior in a rat model of OCD [ 40 ]. Nevertheless, in pediatric obsessive-compulsive disorder, specifically in children with PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), cholinergic interneurons activity in the striatum may contribute to pathophysiology in children with rapid-onset OCD symptoms [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation

et al. 2021

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Background Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. Results There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. Conclusions DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.

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“…, and has been extensively used to study the neural substrates of this behavior 39,[43][44][45]48 , its response to pharmacological manipulations 38,39,43,47,53,54 and to deep brain stimulation 40,46,50 and its modulation by ovarian hormones…”

Section: Discussionmentioning

confidence: 99%

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

Goltseker

Yankelevitch-Yahav

Albelda

et al. 2015

JoVE

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The role of the cholinergic system in the signal attenuation rat model of obsessive-compulsive disorder

Abstract: Acetylcholine does not seem to play a role in the signal attenuation rat model of OCD.

Cited by 8 publications

References 47 publications

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

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