5-HT2A/C receptors do not mediate the attenuation of compulsive checking by mCPP in the quinpirole sensitization rat model of obsessive–compulsive disorder (OCD)

Tucci, Mark C.; Dvorkin‐Gheva, Anna; Johnson, Eric F.; Wong, Michael K.; Szechtman, Henry

doi:10.1016/j.bbr.2014.11.017

Cited by 15 publications

(8 citation statements)

References 34 publications

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“…However, the study did not evaluate 5-HT 2C receptor agonists and, therefore, no data on this mechanism can be gained from their study. Similarly, a report by Tucci et al (23) evaluated the role of 5-HT 2A/C receptors in the anti-OCD-like efficacy of mCPP in attenuating quinpirole-induced compulsive checking behaviors in rats. They concluded that mCPP effects were not mediated by 5-HT 2A/C receptors since ritanserin did not block its effects.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

et al. 2017

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Selective serotonin reuptake inhibitors (SSRIs) are the only effective pharmacological treatments for obsessive–compulsive disorder (OCD). Nonetheless, their generally limited efficacy, side-effects, and delayed onset of action require improved medications for this highly prevalent disorder. Preclinical and clinical findings have suggested serotonin2C (5-HT2C) receptors as a potential drug target. Data in rats and mice are presented here on the effects of a novel 5-HT2C receptor agonist ((3S)-3-Methyl-1-[4-(trifluoromethyl)-7-benzofuranyl]-piperazine) (CPD 1) with high potency and full efficacy at 5-HT2C receptors and less potency and partial agonism at 5-HT2A and 5-HT2B receptors. Effects of CPD 1 on consummatory (schedule-induced polydipsia in rats) and non-consummatory behaviors (marble-burying and nestlet-shredding in mice) that are repetitive and non-habituating were studied. We also evaluated the effects of CPD 1 in rats with isoproterenol- and deprivation-induced drinking in rats to compare with the polydipsia studies. The SSRIs, fluoxetine, and chlomipramine decreased the high rates of drinking in rats engendered by a schedule of intermittent food delivery (schedule-induced polydipsia). The effects of fluoxetine, but not of d-amphetamine, were prevented by the selective 5-HT2C receptor antagonist SB242084. The 5-HT2C receptor agonists Ro 60-0175 and CPD 1 also decreased drinking, but unlike the SSRIs and Ro 60-0175, CPD 1 dose-dependently decreased excessive drinking without affecting lever press responses that produced food. The effects of CPD 1 were prevented by SB242084. CPD 1 also suppressed drinking induced by isoproterenol and by water deprivation without affecting normative drinking behavior. CPD 1, like fluoxetine, also suppressed marble-burying and nestlet-shredding in mice at doses that did not affect rotarod performance or locomotor activity. The behavioral specificity of effects of CPD 1 against repetitive and excessive behaviors suggests a potential therapeutic application in OCD.

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Section: Discussionmentioning

confidence: 99%

Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

et al. 2017

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“…In two other preclinical animal models of OCD-that is, quinpirole-induced compulsive checking and spontaneous stereotypy in the deer mouse-mCPP was also reported to modify compulsive-like behavior routines. Indeed, it reverses compulsive behaviors induced by the dopaminergic agonist quinpirole (Tucci et al, 2013), a response that seems unrelated to 5-HT 2A/C receptor functioning (Tucci, Dvorkin-Gheva, Johnson, Wong, & Szechtman, 2015). However, in the case of noninduced compulsive-like behaviors, both mCPP and quinpirole have been shown to attenuate compulsivelike behaviors (Korff et al, 2008).…”

Section: Serotonergic Drugs In Studies Of Marble-burying Behaviormentioning

confidence: 97%

A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive–compulsive disorder: Mapping the way forward

Brouwer

Fick

Harvey

et al. 2018

Cogn Affect Behav Neurosci

126

111

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Rodent marble-burying behavior in the marble-burying test (MBT) is employed as a model or measure to study anxiety-and compulsive-like behaviors or anxiolytic and anticompulsive drug action. However, the test responds variably to a range of pharmacological interventions, and little consensus exists regarding specific methodologies for its execution. Regardless, the test is widely applied to investigate the effects of pharmacological, genetic, and behavioral manipulations on purported behaviors related to the said neuropsychiatric constructs. Therefore, in the present review we attempt to expound the collective translational significance of the MBT. We do this by (1) reviewing burying behavior as a natural behavioral phenotype, (2) highlighting key aspects of anxiety and obsessive-compulsive disorder from a translational perspective, (3) reviewing the history and proof of concept of the MBT, (4) critically appraising potential methodological confounds in execution of the MBT, and (5) dissecting responses of the MBT to various pharmacological interventions. We conclude by underlining that the collective translational value of the MBT will be strengthened by contextually valid experimental designs and objective reporting of data.

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“…The non-selective 5HT 1A/2A/2B/2C agonist, m-chlorophenylpiperazine, attenuates deer mouse stereotypy (Korff et al, 2008), as well as suppresses QNP-induced checking in rats (Tucci et al, 2013, 2015). Perseverative locomotor paths are indeed associated with 5HT 1B/1D receptor stimulation (Shanahan et al, 2011).…”

Section: Insights Into Ocd From the Deer Mouse: A Platform For Resmentioning

confidence: 99%

Obsessive-compulsive disorder: Insights from animal models

Szechtman

Ahmari

Beninger

et al. 2017

Neuroscience & Biobehavioral Reviews

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Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests.

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5-HT2A/C receptors do not mediate the attenuation of compulsive checking by mCPP in the quinpirole sensitization rat model of obsessive–compulsive disorder (OCD)

Cited by 15 publications

References 34 publications

Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive–compulsive disorder: Mapping the way forward

Obsessive-compulsive disorder: Insights from animal models

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