Neuropeptide Y (NPY) and its receptors are involved in the regulation of mood, stress, and anxiety. In parallel, NPY signaling may play a vital role in the negative affective state induced by drug withdrawal. This study examined the changes in the transcript levels of NPY, Y1, Y2, and Y5 receptors in the mesocorticolimbic system during chronic nicotine exposure and withdrawal. Rats were administered with nicotine (initial dose: 25 μg/ml, maintenance dose: 50 μg/ml, free base) in drinking water for 12 weeks. Control group received only tap water. In the final week of the study, some of the nicotine-treated animals continued to receive nicotine (0-W), whereas some were withdrawn for either 24 (24-W) or 48 (48-W) h. All animals were decapitated after the evaluation of somatic signs (frequency of gasps, eye blinks, ptosis, shakes, teeth chatter) and the duration of locomotor activity and immobility. mRNA levels of NPY, Y1, Y2, and Y5 receptors in the mesocorticolimbic system were measured by quantitative real-time PCR (qRT-PCR). Results showed that nicotine withdrawal increased overall somatic signs. Moreover, chronic nicotine treatment increased the duration of locomotor activity, whereas withdrawal increased the duration of immobility. qRT-PCR analysis revealed that chronic nicotine treatment increased NPY mRNA levels in the hippocampus. On the other hand, 24- and 48-h withdrawals increased NPY mRNA levels in the amygdala and medial prefrontal cortex (mPFC), Y1 and Y2 mRNA levels in the nucleus accumbens and mPFC, and Y5 mRNA levels in the mPFC. These findings suggest that nicotine withdrawal enhances NPY signaling in the mesocorticolimbic system, which could be an important mechanism involved in regulating the negative affective state triggered during nicotine withdrawal.

神经肽 Y (NPY) 及其受体参与情绪、压力和焦虑的调节。同时，NPY信号可能在药物戒断引起的消极情感状态中发挥重要作用。本研究检查了慢性尼古丁暴露和戒断期间皮质边缘系统中 NPY、Y1、Y2 和 Y5 受体转录水平的变化。大鼠在饮用水中给予尼古丁（初始剂量：25 μg/ml，维持剂量：50 μg/ml，游离碱），持续 12 周。对照组只接受自来水。在研究的最后一周，一些接受尼古丁治疗的动物继续接受尼古丁 (0-W)，而有些则停止 24 (24-W) 或 48 (48-W) 小时。在评估体征（喘息频率、眨眼频率、下垂、颤抖、牙齿颤动）以及运动活动和不动的持续时间。通过定量实时 PCR (qRT-PCR) 测量中皮质边缘系统中 NPY、Y1、Y2 和 Y5 受体的 mRNA 水平。结果表明，尼古丁戒断增加了整体躯体症状。此外，长期尼古丁治疗增加了运动活动的持续时间，而戒断增加了不动的持续时间。qRT-PCR 分析显示，慢性尼古丁治疗增加了海马中的 NPY mRNA 水平。另一方面，24 小时和 48 小时戒断增加了杏仁核和内侧前额叶皮层 (mPFC) 中的 NPY mRNA 水平、伏隔核和 mPFC 中的 Y1 和 Y2 mRNA 水平以及 mPFC 中的 Y5 mRNA 水平。这些发现表明，尼古丁戒断增强了中脑边缘系统中的 NPY 信号传导，