Alhaddad Hasan, Wong Woonyen, Sari Adam T, Crotty Alexander Laura E, Sari Youssef
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, the University of Toledo, Toledo, OH 43614, USA.
Pulmonary and Critical Care Section, VA San Diego Healthcare System, 3350 La Jolla Village Dr, MC 111J, San Diego, CA 92161, USA.
Toxics. 2020 Oct 29;8(4):95. doi: 10.3390/toxics8040095.
Electronic cigarettes (e-cigs) use has been dramatically increased recently, especially among youths. Previous studies from our laboratory showed that chronic exposure to e-cigs, containing 24 mg/mL nicotine, was associated with dysregulation of glutamate transporters and neurotransmitter levels in the brain of a mouse model. In this study, we evaluated the effect of three months' continuous exposure to e-cig vapor (JUUL pods), containing a high nicotine concentration, on the expression of glutamate receptors and transporters in drug reward brain regions such as the nucleus accumbens (NAc) core (NAc-core), NAc shell (NAc-shell) and hippocampus (HIP) in female C57BL/6 mice. Three months' exposure to mint- or mango-flavored JUUL (containing 5% nicotine, 59 mg/mL) induced upregulation of metabotropic glutamate receptor 1 (mGluR1) and postsynaptic density protein 95 (phosphorylated and total PSD95) expression, and downregulation of mGluR5 and glutamate transporter 1 (GLT-1) in the NAc-shell. In addition, three months' exposure to JUUL was associated with upregulation of mGluR5 and GLT-1 expression in the HIP. These findings demonstrated that three-month exposure to e-cig vapor containing high nicotine concentrations induced differential effects on the glutamatergic system in the NAc and HIP, suggesting dysregulation of glutamatergic system activity in mesolimbic brain regions.
近年来，电子烟的使用急剧增加，尤其是在年轻人中。我们实验室之前的研究表明，长期暴露于含24毫克/毫升尼古丁的电子烟中，与小鼠模型大脑中谷氨酸转运体和神经递质水平的失调有关。在本研究中，我们评估了连续三个月暴露于高尼古丁浓度的电子烟烟雾（JUUL烟弹）对雌性C57BL/6小鼠伏隔核（NAc）核心（NAc-core）、NAc壳（NAc-shell）和海马体（HIP）等药物奖赏脑区中谷氨酸受体和转运体表达的影响。连续三个月暴露于薄荷味或芒果味的JUUL（含5%尼古丁，59毫克/毫升）可诱导NAc壳中代谢型谷氨酸受体1（mGluR1）和突触后致密蛋白95（磷酸化和总PSD95）表达上调，以及mGluR5和谷氨酸转运体1（GLT-1）表达下调。此外，连续三个月暴露于JUUL还与HIP中mGluR5和GLT-1表达上调有关。这些发现表明，连续三个月暴露于高尼古丁浓度的电子烟烟雾会对NAc和HIP中的谷氨酸能系统产生不同影响，提示中脑边缘脑区谷氨酸能系统活动失调。
