Almalki Atiah H, Alsaab Hashem O, Alsanie Walaa F, Gaber Ahmed, Alkhalifa Turki, Almalki Ahmad, Alzahrani Omar, Hardy Ana Maria Gregio, Alhadidi Qasim, Shah Zahoor A, Althobaiti Yusuf S
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Addiction and Neuroscience Research Unit, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Healthcare (Basel). 2021 Mar 29;9(4):376. doi: 10.3390/healthcare9040376.
Substance-use disorder is globally prevalent and responsible for numerous social and medical problems. Pregabalin (Lyrica), typically used to treat diabetic neuropathy, has recently emerged as a drug of abuse. Drug abuse is associated with several neuronal changes, including the downregulation of glutamate transporters such as glutamate transporter 1 and cystine/glutamate antiporter. We investigated the effects of N-acetylcysteine, a glutamate transporter 1 and xCT upregulator, on pregabalin addiction using a conditioned place preference paradigm. Pregabalin (60 mg/kg) was found to induce conditioned place preference when compared to a vehicle. A 100 mg/kg dose of N-acetylcysteine was found to block pregabalin-seeking behaviors. These results support previous findings showing that glutamate transporters play an important role in pregabalin-induced seeking behaviors. N-acetylcysteine may represent a beneficial agent in preventing the abuse potential of pregabalin.
物质使用障碍在全球范围内普遍存在，并导致众多社会和医学问题。普瑞巴林（乐瑞卡）通常用于治疗糖尿病性神经病变，最近已成为一种滥用药物。药物滥用与多种神经元变化有关，包括谷氨酸转运体如谷氨酸转运体1和胱氨酸/谷氨酸反向转运体的下调。我们使用条件性位置偏爱范式研究了N-乙酰半胱氨酸（一种谷氨酸转运体1和xCT上调剂）对普瑞巴林成瘾的影响。与溶剂相比，发现普瑞巴林（60毫克/千克）可诱导条件性位置偏爱。发现100毫克/千克剂量的N-乙酰半胱氨酸可阻断对普瑞巴林的觅药行为。这些结果支持了先前的研究结果，即谷氨酸转运体在普瑞巴林诱导的觅药行为中起重要作用。N-乙酰半胱氨酸可能是预防普瑞巴林滥用潜力的有益药物。
