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-苯丙胺和甲基汞会改变成年小鼠对单胺摄取抑制剂的敏感性。

妊娠接触甲基汞（MeHg）（一种环境神经毒剂）和青春期服用d-苯异丙胺（d-AMP）会破坏多巴胺的神经传递并改变成年啮齿动物的自发行为。我们通过评估对急性d-AMP，地昔帕明和氯米帕明（分别针对多巴胺，去甲肾上腺素和5-羟色胺再摄取的药物）的敏感性来确定青春期暴露于MeHg和d-AMP对小鼠单胺神经传递的影响。从出生后第21天到60天（鼠青春期），通过饮用水给雄性C57Bl / 6n小鼠0（对照）或3 ppm MeHg。在每个组中，从出生后第28天到第42天每天一次给小鼠注射d-AMP或生理盐水（ip）。这种暴露方案产生了四个治疗组（n = 10-12 /组）：对照组，d-AMP， MeHg和d-AMP + MeHg。作为成年人 老鼠按固定比例的加固时间表（FR 1、5、15、30、60和120）按动杠杆。建立稳定的行为基线后，成年后可进行ip注射的d-AMP（.3-1.7 mg / kg），地昔帕明（5.6-30 mg / kg）和氯米帕明（5.6-30 mg / kg）的急性腹膜内注射。青春期MeHg暴露增加了饱和率和最短响应时间，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可分离的行为作用。青春期d-AMP增加了对急性d-AMP，地昔帕明和氯米帕明的敏感性。仅青春期MeHg暴露不会改变药物敏感性。青少年d-AMP + MeHg的联合暴露增强了对急性d-AMP和地昔帕明对最短响应时间的影响的敏感性。