Nowakowska Elzbieta, Kus Krzysztof, Florek Ewa, Czubak Anna, Jodynis-Liebert Jadwiga
Department of Pharmacology, Karol Marcinkowski University of Medical Sciences, Rokietnicka 5A, PL 60806 Poznań, Poland.
Hum Exp Toxicol. 2006 Apr;25(4):199-209. doi: 10.1191/0960327106ht611oa.
In experimental and clinical studies, central nicotinic systems have been shown to play an important role in cognitive function. Nicotinic acetylcholine receptors also mediate the reinforcing properties of nicotine (NIC) in tobacco products. A variety of studies have shown that acute treatment with NIC or nicotinic agonists can improve working memory function. Moreover, it is known that the monoaminergic system plays an important role in memory function. And there is evidence suggesting that prolonged use of NIC may exert antidepressant action via nicotinic receptors. The purpose of this study was to investigate the interactions between a novel antidepressant, venlafaxine (VEN), a blocker of noradrenaline and 5-hydroxytryptamine reuptake sites, and pure NIC in the context of antidepressant and memory function in tobacco smoke exposed and nonexposed rats. The animals were subjected to Porsolt's test for testing antidepressant activity and their memory function (spatial memory) was evaluated in the Morris Water Maze Test. In tobacco smoke non-exposed and exposed rats both single and chronic administration of VEN (20 mg/kg po) shortened immobility time. NIC (0.2 mg/kg sc) significantly reduced immobility time on the 1st, 7th and 14th test days in both non-exposed and exposed rats. Combined VEN+NIC treatment in tobacco smoke non-exposed rats reduced immobility too. This effect of the combination of drugs was significantly stronger as compared to the effects obtained after individual administration of VEN or NIC. In the group exposed to tobacco smoke, joint administration of VEN+ NIC induced a significant reduction of immobility as compared to the control and NIC groups. In the Morris Water Maze Test single and chronic administration of VEN, lower values of escape latencies and lower numbers of crossed quadrants were noted in both exposed and non-exposed rats, which indicates improved performance. After administering NIC we could observe improvement of spatial memory in both the exposed and non-exposed group. A similar effect of improvement of spatial memory was observed after joint administration of VEN and NIC. The study results support the involvement of nicotinic systems in memory processes in rats. Memory improvement and antidepressant effects following joint administration of VEN and NIC may depend on nicotinic interactions with monoaminergic systems and VEN may represent a new therapeutic approach to smoking cessation.
在实验和临床研究中，中枢烟碱系统已被证明在认知功能中发挥重要作用。烟碱型乙酰胆碱受体也介导烟草制品中尼古丁（NIC）的强化特性。各种研究表明，急性给予NIC或烟碱型激动剂可改善工作记忆功能。此外，已知单胺能系统在记忆功能中起重要作用。并且有证据表明，长期使用NIC可能通过烟碱型受体发挥抗抑郁作用。本研究的目的是在暴露于烟草烟雾和未暴露于烟草烟雾的大鼠中，研究新型抗抑郁药文拉法辛（VEN）（一种去甲肾上腺素和5-羟色胺再摄取位点的阻滞剂）与纯NIC在抗抑郁和记忆功能方面的相互作用。对动物进行波索尔特试验以测试抗抑郁活性，并在莫里斯水迷宫试验中评估其记忆功能（空间记忆）。在未暴露于烟草烟雾和暴露于烟草烟雾的大鼠中，单次和慢性给予VEN（20mg/kg口服）均缩短了不动时间。NIC（0.2mg/kg皮下注射）在未暴露和暴露大鼠的第1、7和14个试验日显著缩短了不动时间。在未暴露于烟草烟雾的大鼠中，VEN+NIC联合治疗也减少了不动时间。与单独给予VEN或NIC后获得的效果相比，药物组合的这种效果显著更强。在暴露于烟草烟雾的组中，与对照组和NIC组相比，VEN+NIC联合给药导致不动时间显著减少。在莫里斯水迷宫试验中，在暴露和未暴露的大鼠中，单次和慢性给予VEN后，观察到逃避潜伏期值降低和穿过象限的次数减少，这表明表现有所改善。给予NIC后，我们在暴露组和未暴露组中均观察到空间记忆的改善。VEN和NIC联合给药后也观察到类似的空间记忆改善效果。研究结果支持烟碱系统参与大鼠的记忆过程。VEN和NIC联合给药后的记忆改善和抗抑郁作用可能取决于烟碱与单胺能系统的相互作用，并且VEN可能代表一种戒烟的新治疗方法。
