Lack of dopamine D4 receptor affinity contributes to the procognitive effect of lurasidone

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

doi:10.1016/j.bbr.2013.11.036

Cited by 31 publications

(19 citation statements)

References 36 publications

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“…In addition to the other unique binding profiles of other monoamine receptors, the lack of affinity for the dopamine D 4 receptor by LRS might also contribute, at least partly, to its cognitive enhancing effect (Murai et al, 2014[108]).…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.

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Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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“…The ability of a drug to modulate ketamine-induced gamma power has been proposed as a useful index for assessing the therapeutic potential of drugs in treating cognitive deficits in patients with schizophrenia [27,5#4]. Low doses of D4R antagonists reverse working memory deficits induced by stress or chronic PCP administration in monkeys [ 46 , 47 ], but decrease task performance when acutely co-administered with the antipsychotic clozapine or lurasidone [ 44 ]. Also, D4R agonists have the ability to increase gamma power and cognitive performance in normal animals [ 43 , 45 , 53 , 101 – 104 ].…”

Section: Discussionmentioning

confidence: 99%

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

et al. 2017

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Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40–70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus. Additionally, we investigated the ability of drugs targeting the dopamine D4 receptor (D4R) to modify the effects of ketamine on gamma activity as a measure of potential cognitive therapeutic efficacy. Rats were trained to walk on a treadmill to reduce confounds related to hyperactivity after ketamine administration (10 mg/kg s.c.) while recordings were obtained from electrodes chronically implanted in the mPFC and MD thalamus. Ketamine increased gamma LFP power in mPFC and MD thalamus in a similar frequency range, yet did not increase thalamocortical synchronization. Ketamine also increased firing rates and spike synchronization to gamma oscillations in the mPFC but decreased both measures in MD thalamus. Conversely, walking alone increased both firing rates and spike-gamma LFP correlations in both mPFC and MD thalamus. The D4R antagonist alone (L-745,870) had no effect on gamma LFP power during treadmill walking, although it reversed increases induced by the D4R agonist (A-412997) in both mPFC and MD thalamus. Neither drug altered ketamine-induced changes in gamma power or firing rates in the mPFC. However, in MD thalamus, the D4R agonist increased ketamine-induced gamma power and prevented ketamine’s inhibitory effect on firing rates. Results provide new evidence that ketamine differentially modulates spiking and gamma power in MD thalamus and mPFC, supporting a potential role for both areas in contributing to ketamine-induced schizophrenia-like symptoms.

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“…The development of a mouse model of the detour test should enable the usage of rodents to study biochemical and anatomical mechanisms of cognitive functions that were previously investigated only in primates [12,53,54]. Furthermore, monkeys are used in preclinical studies employing the detour test to study cognitive effects of various drugs [55,56].…”

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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Lack of dopamine D4 receptor affinity contributes to the procognitive effect of lurasidone

Cited by 31 publications

References 36 publications

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

Neuronal correlates of ketamine and walking induced gamma oscillations in the medial prefrontal cortex and mediodorsal thalamus

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

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