Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety

Thomas, Alexia M.; Burant, April; Bui, Nghiem; Graham, Deanna; Yuva-Paylor, Lisa A.; Paylor, Richard

doi:10.1007/s00213-009-1466-y

Cited by 604 publications

(622 citation statements)

References 48 publications

(69 reference statements)

Supporting

Mentioning

570

Contrasting

Unclassified

Order By: Relevance

“…This result corroborates the proposal that anxiety and OCD models engage distinct brain mechanisms, with the marble burying behaviour being related to repetitive behaviours instead of anxiety [61].…”

Section: Cannabidiol and Anxietysupporting

confidence: 89%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

375

241

View full text Add to dashboard Cite

Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

show abstract

Section: Cannabidiol and Anxietysupporting

confidence: 89%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

375

241

View full text Add to dashboard Cite

show abstract

“…5B). The serotonergic system has also been implicated in anxiety, repetitive behavior, and hyperactivity; therefore, we also tested PET1-CKO animals using assays that would address these behavioral domains (23)(24)(25). We found no evidence of altered anxiety in the light-dark box exploration task, altered self-grooming behavior in the splash test, or abnormal repetitive behavior in the marble-burying task that was specific to the deletion of Mecp2 in PET1-positive serotonergic neurons (Fig.…”

Section: Deletion Of Mecp2 From Either Th-positive or Pet1-positive Nmentioning

confidence: 89%

Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities

Samaco¹,

Mandel‐Brehm²,

Chao

et al. 2009

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

225

214

View full text Add to dashboard Cite

Rett syndrome (RTT) is characterized by specific motor, cognitive, and behavioral deficits. Because several of these abnormalities occur in other disease states associated with alterations in aminergic neurotransmitters, we investigated the contribution of such alterations to RTT pathogenesis. We found that both individuals with RTT and Mecp2-null mice have lower-than-normal levels of aminergic metabolites and content. Deleting Mecp2 from either TH-positive dopaminergic and noradrenergic neurons or PET1-positive serotonergic neurons in mice decreased corresponding neurotransmitter concentration and specific phenotypes, likely through MeCP2 regulation of rate-limiting enzymes involved in aminergic neurotransmitter production. These data support a cell-autonomous, MeCP2-dependent mechanism for the regulation of aminergic neurotransmitter synthesis contributing to unique behavioral phenotypes.dopamine ͉ norepinephrine ͉ Rett syndrome ͉ serotonin R ett syndrome (RTT, MIM 312750) is an X-linked neurodevelopmental disorder caused, in the vast majority of cases, by mutations in Methyl-CpG Binding Protein 2 (MECP2) (1). RTT primarily affects females, with a milder clinical phenotype correlating with late truncating and some missense mutations (2, 3). It has been suspected that aminergic neurons malfunction in RTT, because the heightened anxiety, aggression, and mood alterations seen in RTT and MECP2 disorders are associated with abnormalities of the serotonergic system in other human disorders (4-6). Rigidity and movement abnormalities are associated with dysfunction of dopaminergic system (7-9). Autonomic dysfunction underlying breathing irregularities could be attributable to decreased norepinephrine (7, 10). Although clinical studies have explored the hypothesis that the aminergic neurotransmitter systems might be altered in RTT, no solid conclusions have been reached. Early work suggested decreased aminergic metabolite levels in the spinal fluid of individuals with RTT (11, 12), but subsequent reports failed to identify such changes (13,14). More recently, one study reported instances of both decreased and increased aminergic metabolite levels in a few individuals with RTT (15). The interpretation of these clinical data are hindered by clinical heterogeneity, small sample sizes, and lack of a sufficient number of controls. To circumvent these problems, we explored the role of the aminergic neurotransmitter system by performing both clinical and animal studies. To determine whether the aminergic neurotransmitter system is altered in RTT, we analyzed the levels of the dopamine metabolite homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in spinal fluid from women who both met the clinical criteria for RTT and had a diseasecausing MECP2 mutation. We also evaluated neurotransmitter changes in a RTT murine model and studied the neurochemical, molecular, and behavioral consequences of deleting Mecp2 from either TH-positive dopaminergic and noradrenergic neurons or PET1-positive serot...

show abstract

“…Twenty black 15 mm glass marbles were placed throughout the cage in an equidistant 4 × 5 array (Thomas, Burant et al. 2009). During testing, each mouse was individually placed in the testing cage for 30 min and allowed to bury marbles freely.…”

Section: Methodsmentioning

confidence: 99%

Deletion of Fmr1 results in sex‐specific changes in behavior

et al. 2017

View full text Add to dashboard Cite

ObjectiveIn this study, we used a systemic Fmr1 knockout in order to investigate both genotype‐ and sex‐specific differences across multiple measures of sociability, repetitive behaviors, activity levels, anxiety, and fear‐related learning and memory.BackgroundFragile X syndrome is the most common monogenic cause of intellectual disability and autism. Few studies to date have examined sex differences in a mouse model of Fragile X syndrome, though clinical data support the idea of differences in both overall prevalence and phenotype between the sexes.MethodsUsing wild‐type and systemic homozygous Fmr1 knockout mice, we assessed a variety of behavioral paradigms in adult animals, including the open field test, elevated plus maze, nose‐poke assay, accelerating rotarod, social partition task, three‐chambered social task, and two different fear conditioning paradigms. Tests were ordered such that the most invasive tests were performed last in the sequence, and testing paradigms for similar behaviors were performed in separate cohorts to minimize testing effects.ResultsOur results indicate several sex‐specific changes in Fmr1 knockout mice, including male‐specific increases in activity levels, and female‐specific increases in repetitive behaviors on both the nose‐poke assay and motor coordination on the accelerating rotarod task. The results also indicated that Fmr1 deletion results in deficits in fear learning and memory across both sexes, and no changes in social behavior across two tasks.ConclusionThese findings highlight the importance of including female subjects in preclinical studies, as simply studying the impact of genetic mutations in males does not yield a complete picture of the phenotype. Further research should explore these marked phenotypic differences among the sexes. Moreover, given that treatment strategies are typically equivalent between the sexes, the results highlight a potential need for sex‐specific therapeutics.

show abstract

Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety

Cited by 604 publications

References 48 publications

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities

Deletion of Fmr1 results in sex‐specific changes in behavior

Contact Info

Product

Resources

About