國家衛生研究院 NHRI:Item 3990099045/14552
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    题名: Beneficial effects of atypical antipsychotics on object recognition deficits after adolescent toluene exposure in mice: involvement of 5-HT(1A) receptors
    作者: Lee, MY;Hsieh, CP;Chan, MH;Chen, HH
    贡献者: Center for Neuropsychiatric Research
    摘要: Background: Inhalant (e.g. toluene) misuse by adolescents has been linked to psychosis and persistent cognitive deficits. Identifying effective strategies to improve cognitive deficits following chronic toluene misuse is critical. 5-HT(1A) receptor has been proposed as a target for the treatment of cognitive deficits.Objectives: We compared the effects of antipsychotics on recognition deficits after adolescent toluene exposure in mice and elucidated the role of 5-HT(1A) receptors in the cognition-improving effects of antipsychotics.Methods: Male NMRI mice (n = 279) received one injection per day of either toluene (750 mg/kg) or corn oil at postnatal days 35-39 and 42-46. Thereafter, the acute and subchronic effects of haloperidol, aripiprazole, or clozapine on toluene-induced recognition deficits were evaluated by novel object recognition test.Results: Acute administration of aripiprazole (p < .05) and clozapine (p < .01), but not haloperidol, significantly attenuated the toluene-induced recognition deficits. Pretreatment with 5-HT(1A) receptor antagonist WAY -100,635 (p < .05) blocked their beneficial effects. Moreover, 5-HT(1A) receptor agonist buspirone (p < .01) ameliorated the toluene-induced recognition deficits, which was reversed by WAY -100,635 (p < .001). Finally, after repeated treatment with clozapine, aripiprazole, and buspirone daily for 14 days, the impaired object recognition in toluene-exposed mice was significantly improved (p < .05) and the beneficial effects lasted for at least 2 weeks (p < .05).Conclusions: The results indicate that clozapine and aripiprazole, which display 5-HT(1A) agonist properties, restored cognitive deficits in mice induced by adolescent toluene exposure. These findings suggest that these antipsychotics should be further explored as a potential treatment option for cognitive deficits in patients with psychosis associated with toluene exposure.
    日期: 2022-11
    關聯: American Journal of Drug and Alcohol Abuse. 2022 Nov 2;48(6):673-683.
    Link to: http://dx.doi.org/10.1080/00952990.2022.2122484
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0095-2990&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000857590700001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85139149467
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