The Effects Of Nicotine And Its Co-administration With Urapidil On Spatial Working Memory In Mice

Neuronal nicotinic receptors have been found to be important in cognitive function in rodents as well as primates including rhesus monkeys and humans. Studies using acute and chronic treatments of nicotine and nicotinic agonist have been shown to improve spatial working memory of animals. Anatomical and behavioral studies support an involvement of central serotonergic (5-hydroxytryptamine,5-HT) systems in higher order cognitive functions. Among the 14 identified serotonergic receptor subtypes, animal studies support an involvement for the 5-HT1A receptor subtype in cognitive functions, particularly in spatial working memory. Both central nicotinic and serotonergic systems play important roles in a variety of cognitive functions; however, the effects of nicotine on three phases of information processing and the interactions of these two systems have not been fully characterized.The animal model give the better method to research the interactions of these two systems. In this study, on the one hand, the effects of nicotine on the acquisiton, retention and retrieval processes of spatial working memory were observed and compared using the Morris water maze (MWM) task. On the other hand, the current study served to determine the impact of a selective 5-HT1A receptor agonist, urapidil, on spatial working memory in mice and the interactions of urapidil with nicotine administration.Experiment 1 were performed on 120 adult mice,which were divided randomly into 6 groups and trained in a working memory version of the MWM to find a new target position (trial 1) with two blocks of four trials per day for twenty consecutive days.On the test day, Nicotine was injected (0.1mg/kg, i.p.) 5 min prior to the the day's first trial in group 1, immediately after the day's first trial in group 2, or 5 min prior to the the day's second trial (retrieval) in group 3. Retrieval (trial 2) was tested 75 min later. The remaining 3 groups were injected with saline for control. Experiment 2 were performed on 64 adult mice, which were divided randomly into 4 groups. Twenty four hours after the test day, the spatial working memory were tested again. Mice were injected either saline or urapidil (40mg/kg, i.p.) 15 min prior to trial 2, and either saline or nicotine (0.1 mg/kg, i.p.) 5 min prior to trial 2. The swimming latency, length, strategy and velocity were recorded.For experiment 1, the time mice in group 1 stayed in the goal quadrant was longer than the saline control, animals in group 3 showed shorter latency than the saline control, indicating that to some extent nicotine improved encoding and retrieval of the spatial working memory.For experiment 2, mice treated with nicotine and urapidil showed significant prolongation of swimming latency than mice treated with nicotine or urapidil alone,indicating that the combination of nicotine and urapidil impaired retrieval of the spatial working memory.In conclusion, these data suggest that nicotine may facilitate the encoding and retrieval of spatial working memory and urapidil may facilitate the retrieval of memory, too. However, when animals were administered with the combination of nicotine and urapidil, the improvement of spatial working memory disappeared, indicating that there is reciprocal inhibition between central nicotinic and serotonergic systems.