Abstract：
Numerous studies have suggested that N-acetylcysteine (NAC), has the potential to suppress drug craving in people with substance use disorder and reduce drug-seeking behaviors in animals. The nucleus accumbens (NAc) plays a crucial role in the brain\'s reward system, with the nucleus accumbens core (NAcore) specifically implicated in compulsive drug seeking and relapse. In this study, we aimed to explore the impact of subchronic NAC administration during the extinction period and acute NAC administration on the electrical activity of NAcore neurons in response to a priming dose of morphine in rats subjected to extinction from morphine-induced place preference (CPP).We conducted single-unit recordings in anesthetized rats on the reinstatement day, following the establishment of morphine-induced conditioned place preference (7 mg/kg, s.c., 3 days), and subsequent drug-free extinction. In the subchronically NAC-treated groups, rats received daily injections of either NAC (50 mg/kg; i.p.) or saline during the extinction period. On the reinstatement day, we recorded the spontaneous activity of NAcore neurons for 15 min, administered a priming dose of morphine, and continued recording for an additional 45 min. While morphine excited most recorded neurons in saline-treated rats, it failed to alter firing rates in NAC-treated rats that had received NAC during the extinction period. For acutely NAC-treated animals, we recorded the baseline activity of NAcore neurons for 10 min before administering a single injection of either NAC (50 mg/kg; i.p.) or saline in rats with no treatment during the extinction. Following 30 min of recording and a priming dose of morphine (1 mg/kg, s.c.), the recording continued for an additional 30 min. The firing activity of NAcore neurons did not show significant changes after morphine or NAC injection. In conclusion, our findings emphasize that daily NAC administration during the extinction period significantly attenuates the morphine-induced increase in firing rates of NAcore neurons during the reinstatement of morphine CPP. However, acute NAC injection does not produce the same effect. These results suggest that modulating glutamate transmission through daily NAC during extinction may effectively inhibit the morphine place preference following the excitatory effects of morphine on NAcore neurons.
摘要：
大量研究表明，N-乙酰半胱氨酸(NAC)有可能抑制药物使用障碍患者的药物渴望，并减少动物的药物寻求行为。伏隔核(NAc)在大脑的奖赏系统中起着至关重要的作用,伏隔核（NAcore）与强迫性药物寻求和复发有关。在这项研究中,我们的目的是探讨在吗啡诱导的位置偏爱(CPP)消退的大鼠中,在消退期间亚慢性NAC给药和急性NAC给药对吗啡引发剂量对NAcore神经元电活动的影响.我们在复健日对麻醉大鼠进行了单单位记录，在建立吗啡诱导的条件性位置偏好(7mg/kg，s.c.,3天),以及随后的无毒品灭绝。在亚慢性NAC治疗组中，在消退期间，大鼠每天注射NAC（50mg/kg；i.p.）或生理盐水。在复职的那一天,我们记录了15分钟的NAcore神经元的自发活动，服用了初始剂量的吗啡，并继续录制45分钟。在生理盐水处理的大鼠中，吗啡刺激了大多数记录的神经元，它未能改变在灭绝期间接受NAC的NAC治疗的大鼠的放电率。对于急性NAC治疗的动物，我们记录了10分钟的NAcore神经元的基线活性，然后在灭绝期间未治疗的大鼠中单次注射NAC（50mg/kg;i.p.）或生理盐水。记录30分钟后，注射吗啡（1mg/kg，s.c.)，记录持续了30分钟。注射吗啡或NAC后，NAcore神经元的放电活性没有显着变化。总之,我们的研究结果强调，在灭绝期间每天给药NAC可显着减弱吗啡在恢复吗啡CPP期间引起的NAcore神经元放电率的增加。然而,急性NAC注射不会产生相同的效果。这些结果表明，在吗啡对NAcore神经元的兴奋作用后，在灭绝期间通过每日NAC调节谷氨酸传递可能会有效抑制吗啡的位置偏好。
