Behavioral Consequences of a Combination of Gad1 Haplodeficiency and Adolescent Exposure to an NMDA Receptor Antagonist in Long-Evans Rats

Fujihara, Kazuyuki; Sato, Terukazu; Higeta, Kazuya; Miyasaka, Yoshiki; Mashimo, Tomoji; Yanagawa, Yuchio

doi:10.3389/fphar.2021.646088

Cited by 2 publications

(1 citation statement)

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“…This rat model is the only one that exhibits a distinct working 10.3389/fncel.2023.1161608 memory deficit among GAD67 knockout/knockdown animals. In contrast, Gad1 −/− rats showed only very mild behavioral changes that did not necessarily match the phenotype of Gad1 −/− mice (Fujihara et al, 2021a). The authors repeatedly exposed Gad1 −/− rats to a low-dose NMDA receptor antagonist during adolescence but did not find as many behavioral abnormalities as Gad1 −/− .…”

Section: Gad67 (Gad1) Knockout Ratsmentioning

confidence: 98%

Beyond the γ-aminobutyric acid hypothesis of schizophrenia

Fujihara

2023

Front. Cell. Neurosci.

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Abnormalities in the γ-aminobutyric acid (GABA) system have been reported in the postmortem brains of individuals with schizophrenia. In particular, the reduction of one of the GABA-synthesizing enzymes, the 67-kDa isoform of glutamate decarboxylase (GAD67), has garnered interest among researchers because of its role in the formation of γ-oscillations and its potential involvement in the cognitive dysfunction observed in schizophrenia. Although several animal models have been generated to simulate the alterations observed in postmortem brain studies, they exhibit inconsistent behavioral phenotypes, leading to conflicting views regarding their contributions to the pathogenesis and manifestation of schizophrenia symptoms. For instance, GAD67 knockout rats (also known as Gad1 knockout rats) exhibit marked impairments in spatial working memory, but other model animals do not. In this review, we summarize the phenotypic attributes of these animal models and contemplate the potential for secondary modifications that may arise from the disruption of the GABAergic nervous system.

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Section: Gad67 (Gad1) Knockout Ratsmentioning

confidence: 98%

Beyond the γ-aminobutyric acid hypothesis of schizophrenia

Fujihara

2023

Front. Cell. Neurosci.

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To Play or Not to Play? Effects of Playmate Familiarity and Social Isolation on Social Play Engagement in Three Laboratory Rat Strains

Orsucci,

Becker,

Ham

et al. 2024

Preprint

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Social play is a motivating and rewarding behavior displayed by juveniles of many mammalian species, including humans and rats. Social play is vital to the development of social skills. Autistic children show less social play engagement which may contribute to their impairments in social skills. There is limited knowledge about what external conditions may positively or negatively influence social play engagement in humans or other animals. Therefore, we determined how two common external conditions, playmate familiarity and social isolation, modulate social play levels and social play defense tactics in juveniles of three common laboratory rat strains: Long-Evans, Sprague-Dawley, and Wistar. Males and females were socially isolated for either 2h or 48h prior to social play testing and were then exposed to either a familiar (cage mate) or novel playmate, creating four testing conditions: 2h-Familiar, 48h-Familiar, 2h-Novel, and 48h-Novel. Both playmate familiarity and social isolation length influenced social play behavior levels and tactics in juvenile rats, but did so differently for each of the three rat strains. Long-Evans played most with a familiar playmate, irrespective of time isolated, Sprague-Dawley played most in the 48h-Familiar condition, and Wistar played the least in the 2h-Familiar condition, but Wistar played more with a novel playmate than Long-Evans and Sprague-Dawley. Analysis of social play tactics by the playmates in response to nape attacks by the experimental rats revealed strain differences with novel playmates. Here, Sprague-Dawley and Wistar defended more nape attacks than Long-Evans. Sprague-Dawley evaded these attacks, thereby shortening body contact. In contrast, Wistar turned to face their playmate attacker and showed more complete rotations, thereby extending body contact and wrestling longer. Role reversals, which increase social play reciprocity and reflect the quality of social play, were higher in Long-Evans and Sprague-Dawley with familiar playmates. Role reversals decreased for Sprague-Dawley but increased for Wistar after 48h isolation. The effects of playmate familiarity or social isolation length on social play levels and tactics were similar across sex for all three strains. In conclusion, we showed that two common external factors (playmate familiarity and social isolation length) that largely vary across social play studies have a major impact on the level and quality of social play in the three rat strains. Strain differences indicate higher level and quality of social play with familiar playmates in Long-Evans, with familiar playmates after short isolation in Sprague-Dawley, and with novel playmates after longer isolation for Wistar. Future research could determine whether strain differences in neuronal mechanisms underlie these condition-induced variations in social play engagement. Our findings are also informative in suggesting that external conditions like playmate familiarity and social isolation length could influence social play levels and social play quality in typical and atypical children.

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Behavioral Consequences of a Combination of Gad1 Haplodeficiency and Adolescent Exposure to an NMDA Receptor Antagonist in Long-Evans Rats

Cited by 2 publications

References 44 publications

Beyond the γ-aminobutyric acid hypothesis of schizophrenia

Beyond the γ-aminobutyric acid hypothesis of schizophrenia

To Play or Not to Play? Effects of Playmate Familiarity and Social Isolation on Social Play Engagement in Three Laboratory Rat Strains

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