Effect of YM992, a Novel Antidepressant With Selective Serotonin Re-uptake Inhibitory and 5-HT2A Receptor Antagonistic Activity, on a Marble-Burying Behavior Test as an Obsessive-Compulsive Disorder Model

Takeuchi, Hiromi; Yatsugi, Shin-ichi; Yamaguchi, Tokio

doi:10.1254/jjp.90.197

Cited by 52 publications

(34 citation statements)

References 11 publications

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“…More telling, SSRIs fail to reduce symptomology in 40-60% of OCD patients (Pallanti and Quercioli 2006), although benzodiazepines were even less effective (Goddard et al 2008). The clear implication is that OCD is a complex disorder that involves multiple systems rather the current emphasis on the serotonin receptor (Egashira et al 2008, Marazziti et al 2010, Takeuchi et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Marble burying as compulsive behaviors in male and female mice

Taylor¹,

Lerch²,

Chourbaji³

2017

Acta Neurobiologiae Experimentalis

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Marble burying is considered an, albeit controversial, animal model of the compulsive like behaviors of obsessive-compulsive disorder (OCD). Hallmark features of OCD patients are similarities and, more prominent, differences from anxiety disorders, e.g., the absence of sex differences and resistance to spontaneous remission. We report an experiment on marble burying by male and female C57/BL6/N mice. Animals were administered either the classic anxiolytic drug, diazepam, that targets the GABA receptor or a "pure" inhibitor of the serotonin transporter, escitalopram, that has been reported to be particularly effective in OCD. A burying paradigm that more precisely mimics the human condition was used, e.g., testing in the home environment, chronic drug exposure and acknowledging individual differences by pre-selecting for high marble burying. Results were that there were no sex differences in groups treated with drugs or in control mice. Both diazepam and escitalopram decreased numbers of marbles buried compared to vehicle-only controls in the absence of correlated changes in anxiety. Diazepam, however, was more effective than escitalopram in suppressing MB. The conclusion is that along with serotonin, GABA is involved in regulating compulsive behaviors. The marble burying paradigm may prove more useful for pharmacological drugs tests of impulsivity or attention deficit because of the involvement of serotonin and GABA in both disorders.

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Section: Discussionmentioning

confidence: 99%

Marble burying as compulsive behaviors in male and female mice

Taylor¹,

Lerch²,

Chourbaji³

2017

Acta Neurobiologiae Experimentalis

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“…However, Slitrk1-deficient mice did not display any abnormalities in the marble-burying behavior test (Supplementary Figure S4f), a paradigm used to detect OCD symptoms as well as anxiety-like behavior in animals. 32,33 Although the behavioral phenotypes of Slitrk1-knockout mice are not fully consistent with those of TS patients, these mice display some of the phenomena of TS patients and may yield insight into the pathogenesis of TS. Tic disorders including TS often are associated with anxiety disorders, mood disorders including major depression and phobias.…”

Section: Discussionmentioning

confidence: 99%

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

et al. 2008

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Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an a2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plusmaze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

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“…By taking advantage of this defensive behavior of rodents, the MBT has been established as a widely used model of anxiety due largely to the observation that "traditional" anxiolytics, such as benzodiazepines, are effective at reducing marble-burying behavior (Broekkamp et al 1986). Treatment with other common antidepressants, such as fluvoxamine, fluoxetine, paroxetine, citalopram, and YM992, are also efficacious in this model (Hirano et al 2004(Hirano et al , 2005Ichimaru et al 1995;Njung'e and Handley 1991a;Shinomiya et al 2005;Takeuchi et al 2002). Marble burying is also regarded as a model for obsessivecompulsive disorder, due to the excessive nature of the behavior, as shown by ethological data (Gyertyan 1995;Londei et al 1998;Njung'e and Handley 1991b;Rapoport 1988), and due to the pharmacological efficacy of clinically applied drugs used for the treatment of obsessive-compulsive disorder (Borsini et al 2002;Broekkamp et al 1989;Njung'e and Handley 1991a, b).…”

Section: Introductionmentioning

confidence: 98%