For over 50 years, the sympathomimetic phenylpropanolamine (PPA; ±-norephedrine) was a primary active ingredient in over-the-counter nasal decongestants for both children and adults and continues to be prevalent in the vast majority of countries today. Previously, we reported that juvenile PPA exposure alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC), impacting the motivational valence of cocaine in later life. The present study employed a combination of in vivo microdialysis and immunoblotting approaches to better understand how juvenile PPA exposure impacts catecholamine and glutamate function within the NAC. For this, C57BL/6J mice were pretreated repeatedly with PPA (0 or 40 mg/kg) during postnatal days 21–33. Starting at 70 days of age, the function and expression of receptors and transporters regulating extracellular dopamine and glutamate were determined. Juvenile PPA pretreatment completely abolished the capacity of selective dopamine and epinephrine reuptake inhibitors to increase NAC levels of both catecholamines, without impacting D2 or α2 receptor regulation of catecholamine release. Juvenile PPA pretreatment facilitated the rise in NAC glutamate elicited by dopamine, norepinephrine and glutamate transporter inhibitors and blunted mGlu2/3 inhibition of glutamate release in this region. These data confirm that juvenile exposure to PPA produces protracted perturbations in the regulation of extracellular catecholamine and glutamate levels within the NAC and further the hypothesis that early exposure to sympathomimetic drugs found in cough, cold and allergy medicines, have long-lasting effects upon neurotransmission within brain regions gating motivation.

50 多年来，拟交感神经苯丙醇胺 (PPA；±-去甲麻黄碱) 是儿童和成人非处方鼻腔减充血剂的主要活性成分，如今在绝大多数国家仍然流行。此前，我们曾报道，青少年 PPA 暴露会改变伏隔核 (NAC) 中儿茶酚胺和氨基酸神经递质系统的发育轨迹，从而影响晚年可卡因的动机价。本研究采用了体内微透析和免疫印迹方法，以更好地了解幼年 PPA 暴露如何影响 NAC 内的儿茶酚胺和谷氨酸功能。为此，C57BL/6J 小鼠在出生后第 21-33 天用 PPA（0 或 40 mg/kg）反复预处理。从 70 日龄开始，确定了调节细胞外多巴胺和谷氨酸的受体和转运蛋白的功能和表达。幼年 PPA 预处理完全消除了选择性多巴胺和肾上腺素再摄取抑制剂增加两种儿茶酚胺 NAC 水平的能力，而不影响 D2 或 α2 受体对儿茶酚胺释放的调节。幼年 PPA 预处理促进了多巴胺、去甲肾上腺素和谷氨酸转运蛋白抑制剂引起的 NAC 谷氨酸的上升，并减弱了该区域谷氨酸释放的 mGlu2/3 抑制。