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Title:	Attenuation of toluene-induced brain stimulation reward enhancement and behavioral disturbances by N-acetylcysteine in mice
Authors:	Wu, Chia-Yen Tsai, Yi-Lin Hsieh, Chung-Pin Wang, Tsui Chin 詹銘煥 Chan, Ming-Huan Chen, Hwei-Hsien
Contributors:	神經科學研究所
Keywords:	Cystine-glutamate antiporter;mGluR2/3;Intracranial self-stimulation;Novel object recognition;Social interaction;Rotarod
Date:	2018-09
Issue Date:	2018-07-24 16:50:02 (UTC+8)
Abstract:	Toluene, a commonly used organic solvent, produces a variety of behavioral disturbances in both humans and animals comparable to noncompetitive N-methyl-D-aspartate receptor (NMDARs) antagonists, such as phencyclidine (PCP). N-acetylcysteine (NAC) is capable of reversing the psychotomimetic effects of PCP via activation of cystine-glutamate antiporters (xCT). The present study examined whether NAC is capable of attenuating the toluene-induced brain stimulation reward enhancement and behavioral manifestations. Male mice received various doses of NAC prior to toluene exposure for assessment of intracranial self-stimulation (ICSS) thresholds, rotarod test, novel object recognition task and social interaction test. NAC ameliorated the lowering of ICSS thresholds, motor incoordination, object recognition memory impairments and social withdrawal induced by toluene. Furthermore, the capacity of NAC to ameliorate acute toluene-induced deficits in object recognition and social interaction was blocked by the xCT inhibitor (S)-4-carboxyphenylglycine and the mGluR2/3 antagonist LY341495. These results indicate that NAC could prevent toluene-induced reward facilitation and behavioral disturbances and its beneficial effects, at least for cognitive function and social interaction, are associated with activation of the xCT and mGluR2/3. These findings show the potential promise for NAC to treat toluene dependence and to prevent toluene intoxication caused by unintentional or deliberate inhalation.
Relation:	Toxicology,Volume 408, Pages 39-45
Data Type:	article
DOI link:	https://doi.org/10.1016/j.tox.2018.06.011
DOI:	10.1016/j.tox.2018.06.011
Appears in Collections:	[Graduate Institute of Neuroscience] Periodical Articles

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