Methamphetamine (MA) abuse remains a public health issue. Prenatal MA exposure (PME) poses a significant health problem, as we know very little about the drug's long-term physiological impact on the developing human brain. We investigated the long-term consequences of early MA exposure using a mouse model that targets the brain growth spurt, which occurs during human third-trimester. Adult mice previously subjected to acute MA during post-natal days 4–9 exhibited hyperactivity during the Open-Field Test, while exhibiting no motor coordination changes during the Rotarod Test. Neonatal MA exposure reduced basal dopamine (DA) uptake rates in adult nucleus accumbens slices compared with saline-injected controls. Although slices from neonatal MA-exposed mice showed no change in evoked DA signals in the presence of MA, they exhibited potentiated non-evoked DA release through DA efflux in response to MA. These data suggest that developmental MA exposure alters brain development to produce long-lasting physiological changes to the adult mesolimbic DA system, as well as altering responses to acute MA exposure in adulthood. This study provides new insights into an important, under-investigated area in drugs of abuse research.

甲基苯丙胺 (MA) 滥用仍然是一个公共卫生问题。产前 MA 暴露 (PME) 会带来严重的健康问题，因为我们对该药物对人类大脑发育的长期生理影响知之甚少。我们使用小鼠模型研究了早期 MA 暴露的长期后果，该模型针对人类妊娠晚期发生的大脑生长突增。先前在出生后 4-9 天接受急性 MA 的成年小鼠在旷场测试期间表现出过度活跃，而在旋转测试期间没有表现出运动协调变化。与注射生理盐水的对照组相比，新生儿 MA 暴露降低了成人伏核切片的基础多巴胺 (DA) 摄取率。尽管新生MA暴露小鼠的切片显示在MA存在下诱发的DA信号没有变化，但它们通过响应MA的DA流出表现出增强的非诱发DA释放。这些数据表明，发育期 MA 暴露会改变大脑发育，从而对成人中脑边缘 DA 系统产生持久的生理变化，并改变成年期对急性 MA 暴露的反应。这项研究为滥用药物研究中一个重要的、尚未充分调查的领域提供了新的见解。