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題名 Increased behavioral and neuronal responses to a hallucinogenic drug after adolescent toluene exposure in mice: effects of antipsychotic treatment
作者 詹銘煥
Chan, Ming-Huan
Mei-YiLee
Bih-FenLin
Hwei-HsienChen
貢獻者 神科所
日期 2020-12
上傳時間 27-Oct-2021 10:57:46 (UTC+8)
摘要 Toluene has been characterized as a non-classical hallucinogen drug through activation of 5-HT2A receptors and antagonism of NMDA receptors. It remains unclear whether psychotic symptoms after long-term and intense toluene exposure are associated with abnormalities in 5-HT2A receptor function. The present study examined whether the responses to a hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) were altered in a mouse model of toluene psychosis. Male NMRI mice were subchronically treated with toluene during adolescence. Reciprocal social interaction test and novel object recognition test were conducted to confirm the persistent behavioral deficits in adulthood. Subsequently, DOI-induced head twitch, c-Fos and Egr-2 expression, field potentials in the medial prefrontal cortex (mPFC), and the levels of 5-HT2A, 5-HT1A and mGlu2 receptors in the mPFC were monitored. Toluene exposure during adolescence produced social and memory impairments and enhanced DOI–induced behavioral, molecular and electrophysiological responses, but did not change the levels of 5-HT2A, 5-HT1A or mGlu2 receptors in the mPFC. Moreover, the effects of haloperidol and risperidone on the behavioral deficits and hyper-responsiveness to DOI after adolescent toluene exposure were compared. When administered after adolescent toluene exposure, risperidone could reverse social withdrawal, cognitive impairment and hypersensitivity to DOI, whereas haloperidol was only beneficial for social withdrawal. These findings suggest that increased functionality of 5-HT2A receptors may play a critical role in solvent-induced psychosis and recommend the antipsychotics with more selective 5-HT2A receptor antagonism as the first-line treatment for solvent-induced psychosis.
關聯 Toxicology, No.445, pp.152602
資料類型 article
DOI https://doi.org/10.1016/j.tox.2020.152602
dc.contributor 神科所
dc.creator (作者) 詹銘煥
dc.creator (作者) Chan, Ming-Huan
dc.creator (作者) Mei-YiLee
dc.creator (作者) Bih-FenLin
dc.creator (作者) Hwei-HsienChen
dc.date (日期) 2020-12
dc.date.accessioned 27-Oct-2021 10:57:46 (UTC+8)-
dc.date.available 27-Oct-2021 10:57:46 (UTC+8)-
dc.date.issued (上傳時間) 27-Oct-2021 10:57:46 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/137552-
dc.description.abstract (摘要) Toluene has been characterized as a non-classical hallucinogen drug through activation of 5-HT2A receptors and antagonism of NMDA receptors. It remains unclear whether psychotic symptoms after long-term and intense toluene exposure are associated with abnormalities in 5-HT2A receptor function. The present study examined whether the responses to a hallucinogenic 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) were altered in a mouse model of toluene psychosis. Male NMRI mice were subchronically treated with toluene during adolescence. Reciprocal social interaction test and novel object recognition test were conducted to confirm the persistent behavioral deficits in adulthood. Subsequently, DOI-induced head twitch, c-Fos and Egr-2 expression, field potentials in the medial prefrontal cortex (mPFC), and the levels of 5-HT2A, 5-HT1A and mGlu2 receptors in the mPFC were monitored. Toluene exposure during adolescence produced social and memory impairments and enhanced DOI–induced behavioral, molecular and electrophysiological responses, but did not change the levels of 5-HT2A, 5-HT1A or mGlu2 receptors in the mPFC. Moreover, the effects of haloperidol and risperidone on the behavioral deficits and hyper-responsiveness to DOI after adolescent toluene exposure were compared. When administered after adolescent toluene exposure, risperidone could reverse social withdrawal, cognitive impairment and hypersensitivity to DOI, whereas haloperidol was only beneficial for social withdrawal. These findings suggest that increased functionality of 5-HT2A receptors may play a critical role in solvent-induced psychosis and recommend the antipsychotics with more selective 5-HT2A receptor antagonism as the first-line treatment for solvent-induced psychosis.
dc.format.extent 5144665 bytes-
dc.format.mimetype application/pdf-
dc.relation (關聯) Toxicology, No.445, pp.152602
dc.title (題名) Increased behavioral and neuronal responses to a hallucinogenic drug after adolescent toluene exposure in mice: effects of antipsychotic treatment
dc.type (資料類型) article
dc.identifier.doi (DOI) 10.1016/j.tox.2020.152602
dc.doi.uri (DOI) https://doi.org/10.1016/j.tox.2020.152602