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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D-1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin
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Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D-1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin

机译：通过与多巴胺D-1受体拮抗剂SCH-23390或血清素5-HT2C激动剂Lorcaserin的慢性尼古丁输注慢性尼古丁输注在大鼠中尼古丁自我管理的持续衰减

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Tobacco addiction each year causes millions of deaths worldwide. Brain nicotinic acetylcholine receptors have been shown to be central to tobacco addiction. Nicotine replacement therapy aids tobacco cessation, but the success rate is still far too low. This may in part be due to the fact that neurons with nicotinic receptors are not the only neural systems involved in tobacco addiction. Interacting neural systems also play important roles in tobacco addiction. Nicotine increases the release of a variety of neurotransmitters, including dopamine and serotonin. Dopamine, in particular dopamine D-1 receptors, has been shown to be involved in the reinforcing action of nicotine. Serotonin through its actions on 5-HT2C receptors has been shown to play a key role in modulating the reinforcement of addictive drugs, including nicotine and alcohol. Combination of treatments could provide greater treatment efficacy. These studies were conducted to evaluate combination therapies utilizing nicotine replacement therapy in conjunction with either a dopamine D-1 receptor antagonist SCH-23390 or a serotonin 5-HT2C receptor agonist, lorcaserin. Female Sprague-Dawley rats were given access to self-administer nicotine via IV infusions. Osmotic pumps were implanted to reproduce the kinetic of chronic nicotine patch therapy. SCH-23390 (0.02 mg/kg) or lorcaserin (0.6 mg/kg) were administered prior to nicotine self-administration sessions. Reproducing earlier findings SCH-23390, lorcaserin and nicotine replacement therapy were effective at reducing IV nicotine self-administration. 5HT(2C) agonist treatment had additive effects with chronic nicotine infusion for significantly lowering nicotine self-administration. This study demonstrates the feasibility of combination of chronic nicotine with therapies targeting non-nicotinic receptors as treatment options for tobacco addiction.
机译：烟草成瘾每年都会导致全世界数百万死亡。脑烟碱乙酰胆碱受体已被证明是烟草成瘾的中心。尼古丁替代治疗艾滋病烟草停止，但成功率仍然太低。这部分是由于烟草受体的神经元不是烟草成瘾的唯一神经系统。互动神经系统也在烟草成瘾中发挥重要作用。尼古丁增加了各种神经递质的释放，包括多巴胺和血清素。已显示多巴胺，特别是多巴胺D-1受体，参与尼古丁的增强作用。已经证明了Serotonin通过其对5-HT2C受体的作用，在调制含有尼古丁和酒精的增强中发挥关键作用。治疗组合可以提供更大的治疗效果。进行这些研究以评估利用尼古丁替代疗法结合多巴胺D-1受体拮抗剂SCH-23390或血清素5-HT2C受体激动剂，Lorcaserin的组合疗法。雌性Sprague-Dawley大鼠通过IV输注可获得自我管理的尼古丁。植入渗透泵再现慢性尼古丁贴剂治疗的动力学。在尼古丁自我给药季节之前施用SCH-23390（0.02mg / kg）或洛根塞仑（0.6mg / kg）。再现早期的发现Sch-23390，Lorcaserin和尼古丁替代疗法在减少IV尼古丁自我给药时有效。 5HT（2C）激动剂治疗对慢性尼古丁输注具有添加剂效应，用于显着降低尼古丁自我给药。本研究表明，慢性尼古丁与靶向非烟碱受体的治疗作为烟草成瘾的治疗选择的可行性。

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