Gestational exposure to methylmercury (MeHg), an environmental neurotoxicant, and adolescent administration of d-amphetamine (d-AMP) disrupt dopamine neurotransmission and alter voluntary behavior in adult rodents. We determined the impact of adolescent exposure to MeHg and d-AMP on monoamine neurotransmission in mice by assessing sensitivity to acute d-AMP, desipramine, and clomipramine, drugs that target dopamine, norepinephrine, and serotonin reuptake, respectively. Male C57Bl/6n mice were given 0 (control) or 3 ppm MeHg via drinking water from postnatal day 21 to 60 (murine adolescence). Within each group, mice were given once-daily injections of d-AMP or saline (i.p.) from postnatal day 28 to 42. This exposure regimen produced four treatment groups (n = 10-12/group): control, d-AMP, MeHg, and d-AMP + MeHg. As adults, the mice lever pressed under fixed-ratio schedules of reinforcement (FR 1, 5, 15, 30, 60, and 120). Acute i.p. injections of d-AMP (.3-1.7 mg/kg), desipramine (5.6-30 mg/kg), and clomipramine (5.6-30 mg/kg) were administered in adulthood after a stable behavioral baseline was established. Adolescent MeHg exposure increased saturation rate and minimum response time, an effect that was mitigated by chronic administration of d-AMP in adolescence. In unexposed mice, the three monoamine reuptake inhibitors had separable behavioral effects. Adolescent d-AMP increased sensitivity to acute d-AMP, desipramine, and clomipramine. Adolescent MeHg exposure alone did not alter drug sensitivity. Combined adolescent d-AMP + MeHg exposure enhanced sensitivity to acute d-AMP's and desipramine's effects on minimum response time. Adolescence is a vulnerable developmental period during which exposure to chemicals can have lasting effects on monoamine function and behavior.

中文翻译：

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青春期暴露于 d-安非他明和甲基汞会改变成年小鼠对单胺摄取抑制剂的敏感性。


妊娠期接触甲基汞 (MeHg)（一种环境神经毒物）和青少年服用 d-安非他明 (d-AMP) 会扰乱多巴胺神经传递并改变成年啮齿动物的自主行为。我们通过评估急性 d-AMP、地昔帕明和氯丙咪嗪（分别针对多巴胺、去甲肾上腺素和血清素再摄取的药物）的敏感性，确定了青少年接触 MeHg 和 d-AMP 对小鼠单胺神经传递的影响。雄性 C57Bl/6n 小鼠在出生后 21 天至 60 天（小鼠青春期）通过饮用水给予 0（对照）或 3 ppm MeHg。在每组中，小鼠从出生后第 28 天到 42 天每天注射一次 d-AMP 或盐水 (ip)。这种暴露方案产生了四个治疗组（n = 10-12/组）：对照组、d-AMP、甲基汞和 d-AMP + 甲基汞。成年后，小鼠杠杆按固定比例的强化计划（FR 1、5、15、30、60 和 120）按下。在建立稳定的行为基线后，在成年期急性腹膜内注射 d-AMP (0.3-1.7 mg/kg)、地昔帕明 (5.6-30 mg/kg) 和氯米帕明 (5.6-30 mg/kg)。青少年接触甲基汞会增加饱和率和最短反应时间，但青少年长期服用 d-AMP 可以减轻这种影响。在未暴露的小鼠中，三种单胺再摄取抑制剂具有不同的行为效应。青少年 d-AMP 对急性 d-AMP、地昔帕明和氯米帕明的敏感性增加。仅青少年接触甲基汞并不会改变药物敏感性。青少年 d-AMP + MeHg 联合暴露增强了对急性 d-AMP 和地昔帕明对最短反应时间影响的敏感性。青春期是一个脆弱的发育时期，在此期间接触化学物质会对单胺功能和行为产生持久影响。