N-acetylcysteine yields sex-specific efficacy for cue-induced reinstatement of nicotine seeking
N-acetylcysteine yields sex-specific efficacy for cue-induced reinstatement of nicotine seeking
复制标题
DOI：
10.1111/adb.12711
复制
发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Gipson, Cassandra D.
中科院分区：
文献类型：
--
作者：
Goenaga, Julianna;Powell, Gregory L.;Gipson, Cassandra D.
女性报告在月经周期的某些阶段更渴望。此外，研究表明，与男性相比，女性吸烟的药物治疗效果可能较低，这可能是由于与卵巢激素水平自然波动的相互作用。N-乙酰半胱氨酸（NAC）是一种药物能化合物，在治疗物质使用障碍和预防复发方面显示出一定的疗效。然而，目前尚不清楚NAC是否对尼古丁复吸治疗具有性别特异性有效性。鉴于NAC在使用雄性大鼠的临床前模型中显示出减少尼古丁复吸的前景，因此有必要探索NAC疗效的潜在性别差异。使用大鼠模型，我们首先研究了NAC治疗（100 mg/kg，ip）在尼古丁戒断和消退训练期间减少雄性和雌性大鼠线索诱导的尼古丁寻求的能力。接下来，我们评估NAC的作用是否对雌性大鼠具有发情周期依赖性。结果表明，NAC治疗后，在消退期间，恢复尼古丁寻求显着降低男性，但不是女性，表明性别特异性的NAC的影响。此外，对于雌性动物，无论发情周期阶段如何，与灭绝相比，溶媒和NAC给药组均显著恢复了尼古丁寻求行为。这些结果表明，在此处评价的剂量下，无论发情周期阶段如何，NAC在降低雌性尼古丁复发方面均无效。这些集体研究结果可能对NAC作为自由骑自行车的女性吸烟者的药物疗法的使用和疗效具有重要的临床意义。
Women report greater craving during certain phases of the menstrual cycle. As well, research indicates that pharmacotherapies for smoking may be less efficacious in women compared with men, which may be due to interactions with natural fluctuations in ovarian hormone levels. N-Acetylcysteine (NAC) is a glutamatergic compound that has shown some efficacy in treating substance use disorders and aids in the prevention of relapse. However, it is unclear whether NAC has sex-specific effectiveness for nicotine relapse treatment. Given that NAC has shown promise to reduce nicotine reinstatement in preclinical models using male rats, the exploration of potential sex differences in the efficacy of NAC is warranted. Using a rat model, we first investigated the ability of NAC treatment (100 mg/kg, ip) during nicotine withdrawal with extinction training to reduce cue-induced nicotine seeking in male and female rats. Next, we assessed whether NAC's effects were estrous cycle-dependent for female rats. Results show that following NAC treatment during extinction, reinstatement of nicotine seeking was significantly decreased in males but not females, indicating a sex-specific effect of NAC. Furthermore, for females, both vehicle- and NAC-treated groups significantly reinstated nicotine-seeking behavior compared with extinction, regardless of estrous cycle phase. These results suggest that NAC is inefficacious in reducing nicotine relapse in females regardless of estrous cycle phase at the dose evaluated here. These collective findings could have important clinical implications for use and efficacy of NAC as a pharmacotherapy for freely cycling women smokers.