Effects of lurasidone on executive function in common marmosets

Murai, Takeshi; Nakako, Tomokazu; Ikejiri, Masaru; Ishiyama, Takeo; Taiji, Mutsuo; Ikeda, Kazuhito

doi:10.1016/j.bbr.2013.02.019

Cited by 22 publications

(9 citation statements)

References 36 publications

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“…Furthermore, monkeys are used in preclinical studies employing the detour test to study cognitive effects of various drugs [55,56]. Previously, pharmacologically-induced dysfunction in detour skills have been used to model cognitive impairments observed in human psychiatric [19,20,23,57] and neurological diseases [15–17].…”

Section: Discussionmentioning

confidence: 99%

Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers

Juszczak

Miller

2016

PLoS ONE

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Detour tasks are commonly used to study problem solving skills and inhibitory control in canids and primates. However, there is no comparable detour test designed for rodents despite its significance for studying the development of executive skills. Furthermore, mice offer research opportunities that are not currently possible to achieve when primates are used. Therefore, the aim of the study was to translate the classic detour task to mice and to compare obtained data with key findings obtained previously in other mammals. The experiment was performed with V-shaped barriers and was based on the water escape paradigm. The study showed that an apparently simple task requiring mice to move around a small barrier constituted in fact a challenge that was strongly affected by the visibility of the target. The most difficult task involved a completely transparent barrier, which forced the mice to resolve a conflict between vision and tactile perception. The performance depended both on the inhibitory skills and on previous experiences. Additionally, all mice displayed a preference for one side of the barrier and most of them relied on the egocentric strategy. Obtained results show for the first time that the behavior of mice subjected to the detour task is comparable to the behavior of other mammals tested previously with free-standing barriers. This detailed characterization of the detour behavior of mice constitutes the first step toward the substitution of rodents for primates in laboratory experiments employing the detour task.

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Section: Discussionmentioning

confidence: 99%

Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers

Juszczak

Miller

2016

PLoS ONE

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“…In addition, it is known that there are gender differences in the pharmacological actions and pharmacokinetics of phencyclidine (Nabeshima et al, 1984) or cognitive performance in this task (Sutcliffe et al, 2007). We used four male and six female common marmosets (Clea Japan Inc.) in an object retrieval with detour task, as we described previously (Murai et al, 2013;Baba et al, 2015;Kotani et al, 2016), to obtain sufficient numbers of welltrained marmosets. There were no gender differences in the basal performance of this task (our unpublished data).…”

Section: Methodsmentioning

confidence: 99%

A Novel Phosphodiesterase 1 Inhibitor DSR-141562 Exhibits Efficacies in Animal Models for Positive, Negative, and Cognitive Symptoms Associated with Schizophrenia

Enomoto

Tatara

Goda

et al. 2019

J Pharmacol Exp Ther

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In our drug discovery program, we identified a novel orally available and brain-penetrant phosphodiesterase (PDE) 1 inhibitor, 3-methyl-7-(tetrahydro-2H-pyran-4-yl)-2-{[trans-4-(trifluoromethyl)cyclohexyl]-methoxy}imidazo[5,1-f][1,2,4]triazin-4(3H)-one (DSR-141562). In the present study, we characterized the preclinical profile of DSR-141562. This compound has preferential selectivity for predominantly brain-expressed PDE1B over other PDE1 family members, and high selectivity for the PDE1 family over other PDE families and 65 other tested biologic targets. Oral administration of DSR-141562 at 10 mg/kg slightly elevated the cGMP concentration, and it potently enhanced the increase of cGMP induced by a dopamine D 1 receptor agonist in mouse brains. The cGMP level in monkey cerebrospinal fluid was also elevated after treatment with DSR-141562 at 30 and 100 mg/kg and could be used as a translational biomarker. Since PDE1B is believed to regulate dopaminergic and glutamatergic signal transduction, we evaluated the effects of this compound using schizophreniarelated behavioral assays. DSR-141562 at 3-30 mg/kg potently inhibited methamphetamine-induced locomotor hyperactivity in rats, while it had only minimal effects on the spontaneous locomotor activity. Furthermore, DSR-141562 at 1-100 mg/kg did not induce any signs of catalepsy in rats. DSR-141562 at 0.3-3 mg/kg reversed social interaction and novel object recognition deficits induced by repeated treatment with an N-methyl-D-aspartate receptor antagonist, phencyclidine, in mice and rats, respectively. In common marmosets, DSR-141562 at 3 and 30 mg/kg improved the performance in object retrieval with detour tasks. These results suggest that DSR-141562 is a therapeutic candidate for positive, negative, and cognitive symptoms in schizophrenia. SIGNIFICANCE STATEMENT This is the first paper showing that a phosphodiesterase 1 inhibitor is efficacious in animal models for positive and negative symptoms associated with schizophrenia. Furthermore, we demonstrated that this compound improved cognitive function in the common marmoset, a nonhuman primate.

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“…This study was based on the methodological approach developed by Roberts and Wallis ( 31 ) (object) and Murai et al ( 32 ) (box) for common marmosets, in which few experimental sessions were used. The overall poor performance of the two groups in both direct and mainly reverse tasks calls into question the protocol used in this study, since other experiments report different levels of training required to learn visual discrimination tasks.…”

Section: Discussionmentioning

confidence: 99%

“…Spinelli et al ( 59 ) report that adult common marmosets usually commit around 50 errors before learning a direct task and about 100 before learning a reverse task. Moreover, with training, marmosets were able to perform visual discrimination tasks and learn reversal tasks in both automated and non-automated working memory tests ( 32 , 60 , 61 ). Thus, the limitations shown by the animals in the present study are likely due to the lower number of trials used in the protocol, as well as the stress induced by acute (isolation for habituation before tests) and/or chronic isolation, which poses an additional challenge, thereby reducing learning.…”

Section: Discussionmentioning

confidence: 99%

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Endocrine and Cognitive Adaptations to Cope with Stress in Immature Common Marmosets (Callithrix jacchus): Sex and Age Matter

et al. 2015

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Phenotypic sex differences in primates are associated with body differentiation during the early stages of life, expressed in both physiological and behavioral features. Hormones seem to play a pivotal role in creating a range of responses to meet environmental and social demands, resulting in better reactions to cope with challenges to survival and reproduction. Steroid hormones actively participate in neuroplasticity and steroids from both gonads and neurons seem to be involved in behavioral modulation in primates. Indirect evidence suggests the participation of sexual steroids in dimorphism of the stress response in common marmosets. This species is an important experimental model in psychiatry, and we found a dual profile for cortisol in the transition from juvenile to subadult, with females showing higher levels. Immature males and females at 6 and 9 months of age moved alone from the family group to a new cage, over a 21-day period, expressed distinct patterns of cortisol variation with respect to range and duration of response. Additional evidence showed that at 12 months of age, males and females buffered the hypothalamic–pituitary–adrenal axis during chronic stress. Moreover, chronic stressed juvenile marmoset males showed better cognitive performance in working memory tests and motivation when compared to those submitted to short-term stress living in family groups. Thus, as cortisol profile seems to be sexually dimorphic before adulthood, age and sex are critical variables to consider in approaches that require immature marmosets in their experimental protocols. Moreover, available cognitive tests should be scrutinized to allow better investigation of cognitive traits in this species.

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Effects of lurasidone on executive function in common marmosets

Cited by 22 publications

References 36 publications

Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers

Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers

A Novel Phosphodiesterase 1 Inhibitor DSR-141562 Exhibits Efficacies in Animal Models for Positive, Negative, and Cognitive Symptoms Associated with Schizophrenia

Endocrine and Cognitive Adaptations to Cope with Stress in Immature Common Marmosets (Callithrix jacchus): Sex and Age Matter

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