University of New Hampshire, Department of Psychology, 15 Academic Way, Durham, NH 03824, United States.
Yale University School of Medicine, Division of Molecular Psychiatry, New Haven, CT 06511, United States.
Neuropharmacology. 2018 Jun;135:487-495. doi: 10.1016/j.neuropharm.2018.03.021. Epub 2018 Mar 28.
N-acetylcysteine and bupropion are two promising candidate medications for treatment of substance use disorder. The effects of N-acetylcysteine or bupropion on methamphetamine self-administration of female rats are not well understood. To fill this gap, this study assessed the effects of N-acetylcysteine (0, 30, 60, or 120 mg/kg) and bupropion (0, 10, 30, and 60 mg/kg) on methamphetamine self-administration of female rats across the natural estrous cycle. Following a completed dose-response curve, responding for methamphetamine self-administration was extinguished and the effects of N-acetylcysteine or bupropion on methamphetamine-triggered reinstatement was evaluated in separate experiments. N-acetylcysteine did not decrease responding maintained by methamphetamine or methamphetamine-triggered reinstatement. Bupropion significantly decreased methamphetamine self-administration and methamphetamine-triggered reinstatement in female rats with highest dose (60 mg/kg) also significantly decreasing general chamber activity. In a companion experiment, testing the effect of bupropion on responding maintained by sucrose, we confirmed non-specificity of bupropion's effects as bupropion also decreased responding for sucrose. Considered together, our findings suggest that while N-acetylcysteine has considerable promise for treatment of cocaine dependence it may not generalize to other stimulants like methamphetamine. Furthermore, although bupropion has been shown to effectively decrease methamphetamine self-administration, and presently methamphetamine-triggered reinstatement, its locomotor and reward suppressing effects warrant further investigation including both sexes.
N-乙酰半胱氨酸和安非他酮是两种有前途的治疗物质使用障碍的候选药物。N-乙酰半胱氨酸或安非他酮对雌性大鼠甲基苯丙胺自我给药的影响尚不清楚。为了填补这一空白，本研究评估了 N-乙酰半胱氨酸（0、30、60 或 120mg/kg）和安非他酮（0、10、30 和 60mg/kg）对雌性大鼠自然发情周期内甲基苯丙胺自我给药的影响。在完成剂量反应曲线后，评估了 N-乙酰半胱氨酸或安非他酮对甲基苯丙胺触发复吸的影响。N-乙酰半胱氨酸并没有减少由甲基苯丙胺维持的反应或甲基苯丙胺触发的复吸。安非他酮显著减少了雌性大鼠的甲基苯丙胺自我给药和甲基苯丙胺触发的复吸，最高剂量（60mg/kg）也显著降低了一般室活动。在一项伴侣实验中，测试了安非他酮对蔗糖维持反应的影响，我们证实了安非他酮的作用的非特异性，因为安非他酮也减少了蔗糖的反应。综上所述，我们的研究结果表明，虽然 N-乙酰半胱氨酸在治疗可卡因依赖方面有很大的希望，但它可能不适用于其他兴奋剂，如甲基苯丙胺。此外，尽管安非他酮已被证明能有效减少甲基苯丙胺的自我给药，并且目前能减少甲基苯丙胺触发的复吸，但它的运动和奖励抑制作用值得进一步研究，包括男女两性。
