Methamphetamine (MA) abuse is a worldwide issue that produces health and cognitive effects in the user. MA is abused by some women who then become pregnant and expose their developing child to the drug. Preclinical rodent models demonstrate cognitive deficits following developmental MA exposure, an effect observed in children exposed to MA in utero. To determine if the dopamine receptor D1 (DRD1) is involved in the learning and memory deficits following MA exposure, male Sprague-Dawley rats were treated 4 times daily at 2 h intervals with 0 (saline) or 10 mg/kg of MA from postnatal day (P)6-15, 30 min after 0.5, 1.0, or 2.0 mg/kg SCH23390. Cincinnati water maze testing began on P30, and the high dose of SCH23390 blocked the learning deficits induced by MA with no effect from the lower doses. Morris water maze (MWM) learning deficits following MA were not protected by SCH23390, although there was a non-dose dependent effect in the acquisition phase. Locomotor deficits induced by MA were reversed by all doses of SCH23390. There were no effects of MA on criterion to trial passive avoidance. Taken together, these data show that behaviors that are dependent on the striatum are better protected with the DRD1 antagonist during MA treatment than the hippocampally mediated spatial learning in the MWM. This suggests that multiple mechanisms exist for the deficits induced by neonatal MA administration.

中文翻译：

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在Sprague-Dawley大鼠中暴露新生儿甲基苯丙胺的学习和记忆效应：测试多巴胺受体D1在介导长期效应中的作用。

甲基苯丙胺（MA）滥用是一个全球性问题，会对使用者产生健康和认知影响。MA被某些妇女滥用，然后怀孕并使其发育中的孩子接触该药物。临床前的啮齿动物模型证明了发育性MA暴露后的认知缺陷，这是在子宫内暴露于MA的儿童中观察到的效果。为了确定多巴胺受体D1（DRD1）是否与MA暴露后的学习和记忆障碍有关，雄性Sprague-Dawley大鼠每天两次，每2小时间隔接受4次出生后0（盐水）或10 mg / kg的MA治疗（P）6-15天，0.5、1.0或2.0 mg / kg SCH23390后30分钟。辛辛那提水迷宫测试从P30开始，高剂量的SCH23390阻止了由MA引起的学习缺陷，而低剂量则无影响。尽管在获取阶段存在非剂量依赖性的影响，但MA后的莫里斯水迷宫（MWM）学习缺陷不受SCH23390的保护。所有剂量的SCH23390均可逆转由MA引起的运动功能障碍。MA对试验被动回避的标准没有影响。综上所述，这些数据表明，与MWM中海马介导的空间学习相比，在MA治疗期间，依赖纹状体的行为受到DRD1拮抗剂的保护更好。这表明存在多种机制来解决由新生儿MA给药引起的缺陷。综上所述，这些数据表明，与MWM中海马介导的空间学习相比，在MA治疗期间，依赖纹状体的行为受到DRD1拮抗剂的保护更好。这表明存在多种机制来解决由新生儿MA给药引起的缺陷。综上所述，这些数据表明，与MWM中海马介导的空间学习相比，在MA治疗期间，依赖纹状体的行为受到DRD1拮抗剂的保护更好。这表明存在多种机制来解决由新生儿MA给药引起的缺陷。