Glycyrrhizic acid mitigates the risk of nicotine addiction and nicotine withdrawal: The modulation of kynurenine aminotransferase II

Nicotine, a key addictive compound in cigarettes, contributes to withdrawal symptoms that hinder smoking cessation success. Understanding the neurochemical basis of nicotine addiction and withdrawal is critical for developing effective therapies. This study aimed to investigate the effect of glycyrrhizic acid (GL) on nicotine addiction and nicotine withdrawal, with a focus on the kynurenine pathway and kynurenine aminotransferase 2 (KAT-II) mRNA expression. An experimental study using mouse models to evaluate the behavioral and molecular effects of GL in nicotine-induced addiction and withdrawal. In the addiction model, mice received intraperitoneal injections of NaCl (1.0 mL/kg), nicotine (0.5 mg/kg), or GL (5, 10, or 20 mg/kg), and addiction was evaluated using the conditioned place preference (CPP) test. In the withdrawal model, mice underwent spontaneous withdrawal after chronic nicotine exposure, with GL (10 or 20 mg/kg) administered twice daily. Cognitive performance was evaluated using the T-maze, whereas hippocampal KAT-2 mRNA levels were quantified by real-time polymerase chain reaction. Statistical analysis was performed using ANOVA. Nicotine markedly increased CPP scores, confirming its rewarding effect, whereas GL at all doses significantly reduced these scores. During withdrawal, GL improved cognitive deficits and downregulated the nicotine-induced upregulation of hippocampal KAT-2 mRNA expression. GL effectively reduces nicotine-induced reward and mitigates cognitive deficits during withdrawal, likely through inhibition of KAT-2 mRNA expression in the hippocampus.