Methylmercury (MeHg), an environmental neurotoxicant primarily found in fish, produces neurobehavioral impairment when exposure occurs during gestation. Whether other developmental periods, such as adolescence, display enhanced vulnerability to the behavioral effects of MeHg exposure is only beginning to be explored. Further, little is known about the effects of repeated administration of lysine deacetylase inhibitors, such as sodium butyrate (NaB), on operant behavior. In Experiment 1, male C57BL6/n mice were exposed to 0, 0.3, and 3.0 ppm MeHg (n = 12 each) via drinking water from postnatal days 21 to 60 (murine adolescence). As adults, mice were trained to lever press under an ascending series of fixed-ratio schedules of milk reinforcement selected to enable the analysis of three important parameters of operant behavior using the framework provided by Mathematical Principles of Reinforcement. Adolescent MeHg exposure dose-dependently increased saturation rate, a measure of the retroactive reach of a reinforcer, and decreased minimum response time relative to controls. In Experiment 2, the behavioral effects of repeated NaB administration both alone and following adolescent MeHg exposure were examined. Male C57BL6/n mice were given either 0 or 3.0 ppm MeHg during adolescence and, before behavioral testing, two weeks of once daily i.p. injections of saline or 0.6 g/kg NaB (n = 12 in each cell). Adolescent MeHg exposure again increased saturation rate but did not significantly alter minimum response time. NaB also increased saturation rate in both MeHg exposure groups. These data suggest that the behavioral mechanisms of adolescent MeHg exposure and NaB may be related to the impact of reinforcement on prior responses. Specifically, MeHg and NaB concentrated the effects of reinforcers onto the most recent responses.

中文翻译：

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青少年甲基汞暴露：小鼠丁酸钠的行为机制和作用。

甲基汞（MeHg）是一种主要存在于鱼类中的环境神经毒性物质，在妊娠期间发生暴露时会产生神经行为损害。是否才开始探索其他发展时期（例如青春期）是否对暴露于MeHg的行为具有更高的脆弱性。此外，关于赖氨酸脱乙酰基酶抑制剂（例如丁酸钠（NaB））的重复给药对手术行为的影响知之甚少。在实验1中，雄性C57BL6 / n小鼠从出生后21天到60天（鼠青春期）通过饮用水分别暴露于0、0.3和3.0 ppm MeHg（每人n = 12）。作为成年人 对小鼠进行了训练，使其按照一系列递增的固定比例乳汁强化程序进行杠杆压制，这些时间表被选择为能够使用“增强数学原理”提供的框架来分析操作行为的三个重要参数。与对照组相比，青春期MeHg暴露剂量依赖性地增加了饱和率，这是增强剂的回溯作用的一种度量，并且减少了最小响应时间。在实验2中，研究了重复施用NaB单独和在青少年MeHg暴露后的行为效果。雄性C57BL6 / n小鼠在青春期期间接受0或3.0 ppm的MeHg，在进行行为测试之前，每天两次腹膜内注射生理盐水或0.6 g / kg NaB（每个细胞中n = 12）两次。青春期MeHg暴露再次增加了饱和率，但并未显着改变最小响应时间。NaB还增加了两个MeHg暴露组的饱和率。这些数据表明，青春期MeHg暴露和NaB的行为机制可能与强化对先前反应的影响有关。具体而言，MeHg和NaB将补强剂的作用集中在最新的响应上。