Aim of the research: Glutamate transporter-1 (GLT-1; also known as excitatory amino acid transporter 2) plays an important role in the maintenance of glutamate homeostasis in the synaptic cleft. Down regulation of GLT-1 in the spinal cord has been reported in chronic pain models, which suggests that GLT1 is involved in the development of chronic pain. However, the mechanism by which GLT-1 is down regulated in the spinal cord is still unknown. We hypothesized that norepinephrine is involved in the regulation of GLT-1. The aim of this study was to investigate the effect of norepinephrine on GLT-1 expression in cultured astrocytes. Methods: This study involved both in vivo and in vitro experiments. We first validated changes in GLT-1 mRNA expression in the spinal cord of rats with spared nerve injury (SNI) using real-time RT-PCR. Next, cultured primary astrocytes from the rat spinal cord were stimulated with norepinephrine, and GLT-1 mRNA was subsequently quantitated. RNB cells, an astrocytic cell line, were also stimulated with norepinephrine and other alpha-adrenoceptor agonists. Results: SNI resulted in bilateral downregulation of GLT-1 in rat spinal cord. The in vitro study showed that norepinephrine and phenylephrine dose-dependently downregulated GLT-1 in primary astrocytes and RNB cells. Furthermore, the effect of norepinephrine was reversed by an alpha-adrenoceptor antagonist. Conclusion: Norepinephrine downregulates GLT-1 mRNA expression in astrocytes via the alpha(1)-adrenoceptor. Our results provide new insight into the mechanisms involved in downregulation of GLT-1 in the chronic pain models. (C) 2018 Elsevier Inc. All rights reserved.