PDF(Pubmed)
Abstract：
Nicotine smoking contributes to many preventable disabilities, diseases and deaths. Targeting nicotine reward and withdrawal is a basis for the majority of smoking cessation pharmacotherapies. Due to the emergence of interest in 5-HT2A receptor modulators for numerous psychiatric disorders, we investigated the effect of nelotanserin, a 5-HT2A receptor inverse agonist, on nicotine reward and withdrawal in ICR mice. In nicotine-dependent mice, nelotanserin dose-dependently reduced somatic signs of nicotine withdrawal and thermal hyperalgesia as measured in the hot plate test. However, nelotanserin had no effect on anxiety-like behavior and failed to reduce nicotine reward as measured in the conditioned place preference test. Our results suggest that inverse agonism of the 5-HT2A receptor may be a feasible novel mechanism for smoking cessation by reducing both physical withdrawal and thermal hyperalgesia associated with nicotine abstinence but may require complementary pharmacotherapies targeting affective and reward-associated decrements to improve cessation outcomes.
摘要：
尼古丁吸烟有助于许多可预防的残疾，疾病和死亡。针对尼古丁奖励和戒断是大多数戒烟药物疗法的基础。由于对许多精神疾病的5-HT2A受体调节剂的兴趣的出现，我们调查了奈坦色林的作用，一种5-HT2A受体反向激动剂，ICR小鼠的尼古丁奖励和戒断。在尼古丁依赖的小鼠中，如热板测试中所测量的，奈坦色林剂量依赖性地减少了尼古丁戒断和热痛觉过敏的躯体迹象。然而,Nelotanserin对焦虑样行为没有影响，并且在条件性位置偏好测试中无法降低尼古丁奖励。我们的结果表明，5-HT2A受体的反向激动作用可能是戒烟的一种可行的新机制，可以减少与尼古丁戒断相关的物理戒断和热痛觉过敏，但可能需要针对情感和奖赏相关的减少的补充药物治疗来改善戒烟结果。
