针对GPR3作为一种用于戒烟治疗的新方法
Allison S Mogul1, Kendyl N Laumann1, Malia Bautista1
1Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, USA.
概括
一种新的G蛋白结合受体3 (GPR3) 激动剂,RTI-19318-32,有效地降低了小鼠的尼古丁摄入量,显示出开发新型尼古丁戒断疗法的前景.
科学领域:
- 神经科学
- 药理学
- 关于成的研究
背景情况:
- 烟草使用是全球可预防死亡的主要原因.
- 目前的尼古丁戒断辅助药物长期有效性有限.
- G蛋白结合受体3 (GPR3) 在对尼古丁依赖至关重要的脑部区域表达.
研究的目的:
- 研究GPR3作为戒烟的治疗点.
- 评估一种新型GPR3激动剂RTI-19318-32在小鼠中减少尼古丁自给的疗效.
主要方法:
- 给自行静脉注射尼古丁的小鼠使用RTI-19318-32.
- 评估RTI-19318-32对尼古丁摄入量,食物强化,焦虑和运动的影响.
- 使用GPR3淘汰小鼠来确认受体特异性.
- 检查了GPR3与尼古丁乙胆受体 (nAChR) 在中枢的habenula的同位点.
主要成果:
- 在所有测试剂量中,RTI-19318-32显著减少了雄性和雌性小鼠的尼古丁摄入量.
- 该化合物对GPR3具有选择性,但对GPR3淘汰小鼠的尼古丁摄入没有影响.
- 较高剂量的RTI-19318-32影响了食物强化,但没有影响基线食物消耗,而较低剂量的RTI-19318-32则对尼古丁摄入有选择性.
- 发现GPR3的表达与中部 Habenula 中的nAChR子单元共定位.
结论:
- 通过RTI-19318-32等激动剂激活GPR3受体对降低尼古丁消耗具有功能意义.
- GPR3是开发新型尼古丁戒断药物的有希望的治疗标.
- 针对GPR3与特定电路的接触可能会调节尼古丁消费的冲动.
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