Bombardi Cristiano, Delicata Francis, Tagliavia Claudio, Grandis Annamaria, Pierucci Massimo, Marino Gammazza Antonella, Casarrubea Maurizio, De Deurwaerdère Philippe, Di Giovanni Giuseppe
Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064 Ozzano dell'Emilia, Italy.
Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD2080 Msida, Malta.
Int J Mol Sci. 2021 Apr 30;22(9):4775. doi: 10.3390/ijms22094775.
Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HTR has emerged as a promising drug target for smoking cessation. The 5-HTRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HTR agonist Ro 60-0175 (5-640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HTR-immunoreactive (IR) area while decreasing the number of 5-HTR-IR neurons in the LHb. On the other hand, chronic nicotine increased both the 5-HTR-IR area and 5-HTR-IR LHb neurons in the LHb. Western blot analysis confirmed these findings and further revealed an increase of 5-HTR expression in the medial prefrontal cortex after chronic nicotine exposure not detected by the immunohistochemistry. Altogether, these data show that acute and chronic nicotine exposure differentially affect the central 5-HTR function mainly in the LHb and this may be relevant in nicotine addiction and its treatment.
血清素（5-羟色胺，5-HT）在中枢神经系统的某些尼古丁作用中起着重要作用。在所有5-HT受体（5-HTRs）中，5-HTR已成为戒烟的一个有前景的药物靶点。外侧缰核（LHb）内的5-HTRs可能对尼古丁成瘾至关重要。在此我们表明，急性给予酒石酸尼古丁（2mg/kg，腹腔注射）后，5-HTR激动剂Ro 60-0175（5-640μg/kg，静脉注射）可使大鼠体内记录到的LHb中42%的神经元电活动增加。相反，慢性尼古丁处理（6mg/kg/天，腹腔注射，持续14天）后，Ro 60-0175无法影响LHb神经元放电。此外，急性尼古丁暴露增加了LHb中5-HTR免疫反应性（IR）区域，同时减少了5-HTR-IR神经元的数量。另一方面，慢性尼古丁增加了LHb中5-HTR-IR区域和5-HTR-IR LHb神经元的数量。蛋白质印迹分析证实了这些发现，并进一步揭示了慢性尼古丁暴露后内侧前额叶皮质中5-HTR表达的增加，这是免疫组织化学未检测到的。总之，这些数据表明，急性和慢性尼古丁暴露对主要在LHb的中枢5-HTR功能有不同影响，这可能与尼古丁成瘾及其治疗有关。
