Boomhower Steven R, Newland M Christopher
Department of Psychology.
Exp Clin Psychopharmacol. 2017 Apr;25(2):64-73. doi: 10.1037/pha0000107. Epub 2017 Mar 13.
Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic -amphetamine (-AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two -AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10-12/group): control, MeHg-AMP, and MeHg + -AMP. MeHg exposure (via drinking water) spanned postnatal days 21-59 (the murine adolescent period), and once daily intraperitoneal injections of -AMP or saline spanned postnatal days 28-42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following 2 SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, -AMP, and MeHg + -AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + -AMP exposure. MeHg + -AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic -AMP administration. (PsycINFO Database Record
青春期与多巴胺神经传递的持续成熟有关，并且在许多精神疾病的病因中起作用。青少年接触会扭曲多巴胺神经传递的神经毒物，如甲基汞（MeHg），可能会改变慢性给予苯丙胺（-AMP）对逆向学习和注意力转换的影响。将雄性C57Bl/6n小鼠随机分为两个MeHg暴露组（0 ppm和3 ppm）和两个-AMP暴露组（生理盐水和1 mg/kg/天），产生四个治疗组（每组n = 10 - 12）：对照组、MeHg-AMP组和MeHg + -AMP组。MeHg暴露（通过饮用水）涵盖出生后第21 - 59天（小鼠青春期），每天一次腹腔注射-AMP或生理盐水涵盖出生后第28 - 42天。成年后，小鼠接受空间辨别逆转（SDR）任务训练，其中按压杠杆的空间位置预测强化。经过2次SDR后，开始视觉辨别任务（维度外转换），其中杠杆上方刺激光的存在预测强化。使用逻辑函数对反应进行建模，该函数估计行为转变的速率（斜率）和完成一半转变所需的试验次数（半最大值）。MeHg、-AMP和MeHg + -AMP暴露增加了第二次逆转时半最大值的估计值。MeHg暴露增加了维度外转换后的半最大值并降低了斜率项，但MeHg + -AMP暴露后未出现这些影响。MeHg + -AMP暴露在逆转后产生更多的持续性错误和遗漏。青少年接触MeHg可以改变慢性给予-AMP的行为影响。（PsycINFO数据库记录）
