Nianpanich Saranda, Rodsiri Ratchanee, Islamie Ridho, Limpikirati Patanachai, Thanusuwannasak Thanundorn, Vajragupta Opa, Kanasuwan Apinan, Sarasamkan Jiradanai
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Research Unit, Chulalongkorn University, Bangkok, 10330, Thailand.
Psychopharmacology (Berl). 2024 Dec;241(12):2485-2495. doi: 10.1007/s00213-024-06675-w. Epub 2024 Aug 23.
Substance use disorders (SUDs) represent a significant global health concern, demanding the development of effective pharmacological treatments. To address this, an investigation was conducted to examine the anti-addictive properties of two compounds, (S)-T1 and (S)-T2, which specifically target the α3β4 nicotinic acetylcholine receptor (nAChR).
The effects of (S)-T1 and (S)-T2 on nicotine-induced conditioned place preference (CPP), locomotor activity and dopamine levels in particular brain regions associated to addiction were investigated and compared in male C57BL/6N mice.
The results demonstrate that neither (S)-T1 nor (S)-T2 induced place conditioning or conditioned place aversion (CPA), suggesting the absence of rewarding or aversive effects. Both compounds significantly attenuated nicotine-induced CPP, with (S)-T1 exhibiting a dose-dependent effect. Furthermore, the co-administration of (S)-T2 (10 mg/kg) with nicotine markedly reduced locomotor activity compared to nicotine treatment alone. Additionally, dopamine analysis revealed that nicotine increased dopamine levels in the nucleus accumbens (NAc) and dorsal striatum, whereas the co-administration of (S)-T1 (1, 3, and 10 mg/kg) and (S)-T2 (10 mg/kg) significantly decreased dopamine levels in these brain regions. No significant effects were observed in the prefrontal cortex (PFC).
These findings suggest that (S)-T1 and (S)-T2 hold promise for treating nicotine addiction by attenuating nicotine-induced CPP and modulating dopamine release in key reward-related brain regions. Further research is needed to gain insights into the underlying mechanisms behind their anti-addictive effects and substantiate their potential for treating nicotine addiction.
物质使用障碍（SUDs）是一个重大的全球健康问题，需要开发有效的药物治疗方法。为解决这一问题，开展了一项研究，以检验两种化合物（S）-T1和（S）-T2的抗成瘾特性，这两种化合物专门作用于α3β4烟碱型乙酰胆碱受体（nAChR）。
在雄性C57BL/6N小鼠中研究并比较了（S）-T1和（S）-T2对尼古丁诱导的条件性位置偏爱（CPP）、运动活性以及与成瘾相关的特定脑区多巴胺水平的影响。
结果表明，（S）-T1和（S）-T2均未诱导位置条件化或条件性位置厌恶（CPA），表明不存在奖赏或厌恶效应。两种化合物均显著减弱了尼古丁诱导的CPP，其中（S）-T1表现出剂量依赖性效应。此外，与单独给予尼古丁相比，（S）-T2（10mg/kg）与尼古丁共同给药显著降低了运动活性。另外，多巴胺分析显示，尼古丁增加了伏隔核（NAc）和背侧纹状体中的多巴胺水平，而（S）-T1（1、3和10mg/kg）和（S）-T2（10mg/kg）共同给药显著降低了这些脑区的多巴胺水平。在前额叶皮质（PFC）中未观察到显著影响。
这些发现表明，（S）-T1和（S）-T2有望通过减弱尼古丁诱导的CPP并调节关键奖赏相关脑区的多巴胺释放来治疗尼古丁成瘾。需要进一步研究以深入了解其抗成瘾作用背后的潜在机制，并证实其治疗尼古丁成瘾的潜力。
