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Objectives: It has been shown that nicotine plays a significant role in improvement of memory. Based on this finding, nicotinic drugs are being developed for possible use as co-treatments for cognitive impairment in some kinds of mental disorders. However, past studies have mostly emphasized working memory function following acute administration of nicotine and the few studies concerned with reference memory have shown no significant effects. As the 8-Arm Radial Maze, which has been used in most of the studies in this field, provides a lower task difficulty, the present article aims to replicate previous studies with a specific emphasis on reference memory using a 12-Arm Radial Maze which provides a higher level of cognitive task demands.
Methods: Three groups of male Wistar rats were used. The rats were subcutaneously injected with three doses of nicotine 20 min prior to the start of each trial on the Radial- Arm Maze. The first group was injected with 0.1 mg/kg nicotine solution, the second group was injected with 0.4 mg/kg , and the third group was the control which received saline. The spatial memory of the rats was tested on a 12-Arm Radial Maze. The arm choices were recorded when the rat had placed all of its paws beyond the threshold at the proximal end of the arm. Each session of the testing continued until the rat ate all 6 baits or until the maximum time of 6 minutes was over. There was at least 24 hours between drug injections during which time the rats were not tested.
Results: The results of repeated analysis of variance showed a significant difference in working memory errors among the three groups, but there was no significant difference in reference memory errors between the groups. An inverted U-shaped dose-effect curve was seen for reference memory which showed that nicotine first results in increased reference memory errors and then, perhaps because of the effect of training, the number of errors decreased.
Conclusions: The current study suggests a negative correlation between acute consumption of nicotine and long-term spatial performance on a 12-Arm Radial Maze, which contradicts the former assumption on an 8-Arm Radial Maze. This finding also emphasizes the different mechanisms underlying working and reference memory that should be considered in pharmacotherapeutic interventions with nicotinic drugs and other drugs for memory impairments in various mental disorders.