Yokukansankachimpihange and Kamishoyosan attenuate aggressive behavior induced by nicotine withdrawal in mice

<p>Objectives: We aimed to examine the ameliorative effects of Yokukansankachimpihange (YKSCH) and Kamishoyosan (KSS), traditional Japanese medicines prescribed for irritability, on nicotine withdrawalinduced aggressive behaviors in mice.<br>Methods: We established a nicotine self-administration model in C57BL/6J mice, which show increased nicotine preference and aggressive behavior after nicotine withdrawal. In this model, either YKSCH (750 mg/kg) or KSS (600 mg/kg) was administered orally once daily for 7 days after nicotine withdrawal. Subsequently, we assessed the ameliorative effects of YKSCH and KSS on aggressive behavior during nicotine cessation by administering the resident-intruder test and measuring aggressive biting behavior.<br>Results: Nicotine-treated mice exhibited aggressive behavior more frequently than wild-type mice. However, in the resident-intruder test, the duration of aggressive behavior was significantly reduced in KSS-treated mice, but not in nicotine-treated mice ( p < 0.001). Moreover, YKSCH-treated mice tended to decrease the total offence time ( p = 0.088). Consistent with these findings, either YKSCH or KSS treatment improved the intensity of aggressive biting behavior as measured by the Aggression Response Meter (YKSCH: p < 0.05, KSS: p < 0.01).<br>Conclusions: YKSCH and KSS attenuated nicotine withdrawal-induced aggressive behaviors, suggesting that these traditional medicines may provide a new supportive intervention for smoking cessation.</p>