Abstract
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.