Potential Benefits of N-Acetylcysteine in Preventing Pregabalin-Induced Seeking-Like Behavior

Atiah H Almalki; Hashem O Alsaab; Walaa F Alsanie; Ahmed Gaber; Turki Alkhalifa; Ahmad Almalki; Omar Alzahrani; Ana Maria Gregio Hardy; Qasim Alhadidi; Zahoor A Shah; Yusuf S Althobaiti

doi:10.3390/healthcare9040376

Potential Benefits of N-Acetylcysteine in Preventing Pregabalin-Induced Seeking-Like Behavior

Healthcare (Basel). 2021 Mar 29;9(4):376. doi: 10.3390/healthcare9040376.

Authors

Atiah H Almalki^{1

2}, Hashem O Alsaab^{2

3}, Walaa F Alsanie^{2

4}, Ahmed Gaber^{2

5}, Turki Alkhalifa⁶, Ahmad Almalki⁶, Omar Alzahrani², Ana Maria Gregio Hardy⁷, Qasim Alhadidi⁸, Zahoor A Shah⁹, Yusuf S Althobaiti^{2

6

10}

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Addiction and Neuroscience Research Unit, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁴ Department of Clinical Laboratories Sciences, The Faculty of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁶ Ministry of Interior, General Directorate of Narcotics Control, General Administration for Precursors and Laboratories, Riyadh 11564, Saudi Arabia.
⁷ Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA.
⁸ Department of Anesthesiology, Perioperative and Pain Medicine, Stanford Medical School, Stanford University, Stanford, CA 94305, USA.
⁹ Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
¹⁰ Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

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.

Keywords: CPP; GLT-1; NAC; addiction; pregabalin; xCT.

Grants and funding

1-439-6079./Taif University