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Effects of lurasidone on ketamine-induced joint visual attention dysfunction as a possible disease model of autism spectrum disorders in common marmosets

Published on Nov 1, 2014in Behavioural Brain Research2.77
· DOI :10.1016/j.bbr.2014.08.032
Tomokazu Nakako7
Estimated H-index: 7
,
Takeshi Murai6
Estimated H-index: 6
+ 8 AuthorsKazuhito Ikeda6
Estimated H-index: 6
Abstract
Abstract Infants with autism have difficulties performing joint visual attention (JVA), defined as following another person's pointing gesture and gaze. Some non-human primates (NHPs) can also perform JVA. Most preclinical research on autism spectrum disorders (ASD) has used rodents as animal models of this social interaction disorder. However, models using rodents fail to capture the complexity of social interactions that are disrupted in ASD. Therefore, JVA impairment in NHPs might be a more useful model of ASD. The aim of this study was to develop an appropriate and convenient ASD model with common marmosets. We first tested whether marmosets were capable of performing JVA. Subsequently, we administered ketamine, an N -methyl- d -aspartate (NMDA) receptor antagonist, to induce JVA impairment and investigated the effects of lurasidone, a newer antipsychotic agent, on the JVA impairments. An apparatus was constructed using 4 white boxes, which were attached to the corners of a frame. All boxes had a hinged door, and marmosets could easily obtain a reward by pushing the door. An experimenter pointed and gazed at the boxes to inform the marmosets which box contained the reward. Their behavior was scored according to the number of incorrect choices. The JVA score was significantly higher in the cued vs. uncued tasks. Ketamine significantly decreased the JVA score, but lurasidone significantly reversed this effect. These findings suggest that this experimental system could be a useful animal model of neuropsychiatric disorders characterized by NMDA-receptor signaling, including ASD, and that lurasidone might be effective for some aspects of ASD.
  • References (40)
  • Citations (5)
References40
Newest
#1Mei Huang (NU: Northwestern University)H-Index: 22
#2John J. Panos (NU: Northwestern University)H-Index: 1
Last. Herbert Y. Meltzer (NU: Northwestern University)H-Index: 127
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Atypical antipsychotic drugs (AAPDs) have been suggested to be more effective in improving cognitive impairment in schizophrenia than typical APDs, a conclusion supported by differences in receptor affinities and neurotransmitter efflux in the cortex and the hippocampus. More potent serotonin (5-HT)2A than dopamine (DA) D2 receptors antagonism, and direct or indirect 5-HT1A agonism, characterize almost all AAPDs. Blonanserin, an AAPD, has slightly greater affinity for D2 than 5-HT2A receptors. U...
41 CitationsSource
#1Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
#2Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
Last. Mutsuo Taiji (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 24
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Abstract We previously demonstrated among several antipsychotics exhibiting potent dopamine D 2 receptor antagonism that only lurasidone, (1R,2S,3R,4S)- N -[(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1] heptanedicarboximide hydrochloride, improved performance in the object retrieval detour (ORD) task by marmosets. The mechanisms by which only lurasidone causes enhancements in cognitive function have not yet been established; however, most anti...
19 CitationsSource
#1Chao Chuan Wang (KMU: Kaohsiung Medical University)H-Index: 4
#2Hui-Ching Lin (NYMU: National Yang-Ming University)H-Index: 16
Last. Po See Chen (NCKU: National Cheng Kung University)H-Index: 32
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Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of...
18 CitationsSource
#1Jessica A. Burket (EVMS: Eastern Virginia Medical School)H-Index: 17
#2Andrew D. Benson (EVMS: Eastern Virginia Medical School)H-Index: 10
Last. Stephen I. Deutsch (EVMS: Eastern Virginia Medical School)H-Index: 31
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Abstract The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, d -cycloserine, a partial glycine B site agonist that targets the NMDA receptor, was shown to improve the sociability of the Balb/c mouse strain, another proposed genetically inbred model of ASDs. NMDA receptor activation is an importa...
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#1Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
#2Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
Last. Kazuhito Ikeda (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
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Abstract It is considered that functional deficiency of the NMDA receptors in the prefrontal cortex (PFC) is one of the causes of the cognitive impairment observed in schizophrenia. As non-human primates display more developed PFC than rodents, they are considered to be useful experimental animals for improving the predictive validity of models used to discover new drugs for treating cognitive dysfunction. The aim of this study was to develop a convenient model of the cognitive impairment observ...
18 CitationsSource
#1Agnieszka Nikiforuk (PAN: Polish Academy of Sciences)H-Index: 22
#2Tomasz Kos (PAN: Polish Academy of Sciences)H-Index: 18
Last. Piotr Popik (PAN: Polish Academy of Sciences)H-Index: 46
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A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 rec...
55 CitationsSource
#1Takeshi Murai (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
#2Tomokazu Nakako (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 7
Last. Kazuhito Ikeda (Dainippon Sumitomo Pharma Co., Ltd.)H-Index: 6
view all 6 authors...
Abstract Cognitive impairment is one of the major symptoms of schizophrenia, and is considered largely due to dysfunctions in the prefrontal cortex (PFC). Lurasidone, a novel atypical antipsychotic agent with high binding affinity for dopamine D 2 , serotonin 5-HT 7 , 5-HT 2A and 5-HT 1A receptors has been reported to have superior efficacy in rodents’ models of cognitive impairment. However, the beneficial effect of lurasidone on cognitive impairment has not been evaluated in non-human primates...
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#1Michael J. Gandal (UPenn: University of Pennsylvania)H-Index: 31
#2Rachel L. Anderson (UPenn: University of Pennsylvania)H-Index: 1
Last. Steven J. Siegel (UPenn: University of Pennsylvania)H-Index: 55
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Reduced NMDA-receptor (NMDAR) function has been implicated in the pathophysiology of neuropsychiatric disease, most strongly in schizophrenia but also recently in autism spectrum disorders (ASD). To determine the direct contribution of NMDAR dysfunction to disease phenotypes, a mouse model with constitutively reduced expression of the obligatory NR1 subunit has been developed and extensively investigated. Adult NR1neo−/− mice show multiple abnormal behaviors, including reduced social interaction...
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#1Greg C. Carlson (UPenn: University of Pennsylvania)H-Index: 5
There is strong evidence that metabotropic and ionotropic glutamate receptors are affected in autism spectrum disorders (ASD), but there are few candidate genes indicating involvement of these receptors. This suggests that glutamate receptor dysregulation may primarily be involved in the expression of ASD, but is an uncommon etiology. Directly implicated in models of fragile-X with ASD phenotypes is metabotropic glutamate receptor type 5 (mGluR5), which appears to be an effective pharmacologic t...
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#1Eric Courchesne (UCSD: University of California, San Diego)H-Index: 98
#2Peter R. MoutonH-Index: 15
Last. Karen PierceH-Index: 45
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Results Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.901.42; P=.002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P=.003 ) and 29% more in M-PFC ( 0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P=.009). Brain weight in the autistic cases differed from normative mea...
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