Tizabi Yousef, Getachew Bruk, Rezvani Amir H, Hauser Sheketha R, Overstreet David H
Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):398-402. doi: 10.1016/j.pnpbp.2008.09.010. Epub 2008 Sep 19.
A strong positive association between depression and alcoholism is evident in epidemiological studies. Curiously, the incidence of smoking (nicotine intake) is also very high among depressed individuals. Because neuronal nicotinic receptors have been implicated in mood regulation as well as in reinforcing effects of alcohol, it was of interest to determine whether inherent changes in these receptors may be manifested in an animal model that expresses both depressive-like characteristics and high alcohol intake. Thus, Fawn-Hooded (FH) rats along with their control ACI rats were used to measure the density of the high affinity nicotinic receptor in discrete brain regions. Furthermore, the effects of acute and chronic nicotine on depressive-like characteristics of FH rats were also evaluated. Measurements of [(3)H]cytisine binding (selective for alpha4beta2 nicotinic receptor subtype) revealed a reduction in these receptors only in the striatum of FH rats, a result very similar to that observed in selectively-bred alcohol-preferring (P) rats. Administration of nicotine acutely (0.4 mg/kg, sc) resulted in a significant reduction of immobility in the forced swim test (FST) in FH rats only, implying an antidepressant-like effect of nicotine. Another group of FH rats were administered 0.4 mg/kg nicotine (daily, sc) for 14 days and their behavior in the FST was evaluated 22-24 h after the last injection. In this case, nicotine also had a significant antidepressant-like effect in FH rats suggesting no tolerance to nicotine had occurred. The effects of nicotine on FST behavior are very similar to those observed in Flinders Sensitive Line rats, a putative animal model of depression. Together, these findings provide additional evidence for antidepressant-like effects of nicotine and strengthen the postulated association between striatal nicotinic receptors and high alcohol intake. Thus, nicotinic receptors could be suitable targets for the development of novel pharmacotherapy for treatment of depression and possibly alcoholism.
流行病学研究表明，抑郁症与酗酒之间存在明显的强正相关。奇怪的是，抑郁症患者中的吸烟率（尼古丁摄入量）也非常高。由于神经元烟碱受体与情绪调节以及酒精的强化作用有关，因此确定这些受体的内在变化是否会在同时表现出抑郁样特征和高酒精摄入量的动物模型中体现出来很有意义。因此，使用斑点罩帽（FH）大鼠及其对照ACI大鼠来测量离散脑区中高亲和力烟碱受体的密度。此外，还评估了急性和慢性尼古丁对FH大鼠抑郁样特征的影响。[(3)H]金雀花碱结合（对α4β2烟碱受体亚型具有选择性）测量结果显示，仅在FH大鼠的纹状体中这些受体减少，这一结果与在选择性培育的嗜酒（P）大鼠中观察到的结果非常相似。急性给予尼古丁（0.4mg/kg，皮下注射）仅导致FH大鼠在强迫游泳试验（FST）中的不动时间显著减少，这意味着尼古丁具有抗抑郁样作用。另一组FH大鼠每天皮下注射0.4mg/kg尼古丁，持续14天，并在最后一次注射后22 - 24小时评估它们在FST中的行为。在这种情况下，尼古丁对FH大鼠也有显著的抗抑郁样作用，表明未出现对尼古丁的耐受性。尼古丁对FST行为的影响与在弗林德斯敏感品系大鼠（一种假定的抑郁症动物模型）中观察到的非常相似。总之，这些发现为尼古丁的抗抑郁样作用提供了更多证据，并加强了纹状体烟碱受体与高酒精摄入量之间的假设关联。因此，烟碱受体可能是开发用于治疗抑郁症以及可能治疗酗酒的新型药物疗法的合适靶点。
