Nicotine improves memory in an object recognition task in rats

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Abstract

Nicotine was investigated for its mnemonic effect in a two trials object recognition task. In the first trial, two copies of the same object were presented. In the second trial (24 h after), one of the familiar object and a new object were presented. The time spent exploring the new object by control rats was not significantly different from the exploration time of the familiar object, indicating that they did not remember the familiar object. Rats injected with nicotine before the first trial, after the first trial or before the second trial spent more time in exploring the new object than the familiar one at the second trial. These results suggest that, in normal rats, acute nicotine enhances acquisition, consolidation and restitution of the information in an object recognition task.

Introduction

Evidence for the role of the brain nicotinic acetylcholine receptors in memory and cognition is now overwhelming and has been reviewed by number of authors Decker et al., 1995, Levin, 1992, Stolerman et al., 1995. Nicotine has been reported to improve information processing and/or memory in human Le Houezec et al., 1994, Warbuton et al., 1992 and in nonhuman primates (Buccafusco et al., 1995). Moreover, postmortem studies indicate that nicotine binding sites in human brain are affected by ageing or by Alzheimer disease (Nordberg et al., 1992). Experiments on rodents demonstrate that nicotine injections counteract memory deficits induced by various brain lesions Decker et al., 1992, Grigoryan et al., 1994, or by muscarinic or nicotinic antagonists (Zarrindast et al., 1996), and can also improve memory in intact rats or mice Haroutunian et al., 1985, Sansone et al., 1991, Zarrindast et al., 1996. However, beneficial memory effects of nicotine remain discussed, since some investigators have not seen nicotine-induced improvements and some have seen deficits Mundy and Iwamoto, 1988, Sahgal et al., 1990. Numerous factors, i.e., genetic factors, nature of the tasks or animals’ age could explain differential effects of nicotine on memory in normal rats (Arendash et al., 1995, Levin and Torry, 1996, Socci et al., 1995; see also Levin, 1992, for review). A recent study (Levin et al., 1997) demonstrated that in a 16-arm radial maze, working memory was improved by nicotine and disrupted by the nicotinic antagonist mecamylamine, while reference memory was not altered by both drugs. However, other authors did not find nicotine-induced memory improvement in matching or nonmatching-to-sample tasks that are also considered to measure working memory (Sahgal et al., 1990).

The current study examined the effect of nicotine on the performance of rats submitted to an object recognition task, that has been considered to be a pure working memory task (Ennaceur and Delacour, 1988). As reported in previous experiments, rats are able to discriminate between a familiar object and a new object 1 h or less, but not 24 h, after the presentation of the familiar object Deschaux et al., 1997, Ennaceur et al., 1989, Puma and Bizot, 1998. The effect of nicotine was examined on the acquisition of the information, on the consolidation of memory that takes place shortly after the acquisition, and on the restitution of the information. Since it was expected that nicotine would improve memory, a retention interval of 24 h separated the acquisition trial and the retention trial.

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Materials and methods

The animals used were male Wistar rats (Janvier, France) weighting 180–220 g. They were housed five per cage in a regulated environment with a 12 h light/dark cycle. They had free access to food and water. The animals were used for experimentation after adaptation to laboratory conditions for at least 5 days.

The apparatus of the object recognition task was an open box made of Plexiglas (60 cm L; 60 cm W; 30 cm H). The objects to be discriminated were an hemisphere in painted black wood and a

Results

In experiment 1, the exploration time was not significantly different between T1 and T2 (session effect: F(1,93)=0.7; NS), and nicotine did not significantly modify the total exploration time in T1 and T2 (dose effect: F(4,93)=0.4; NS; dose×session: F(1,93)=1.7; NS; see Table 1). Fig. 1A shows that nicotine increased the difference of exploration time between the new object and the familiar object in T2 (F(4,93)=4.1; P<0.01). This effect was statistically significant for the doses of 0.2 mg/kg (

Discussion

Past results indicated that rats spend more time in exploring a new object than a familiar object when the interval between the sample trial and the choice trial is 1 h or less, but not if this interval is 24 h Deschaux et al., 1997, Puma and Bizot, 1998. In this respect, our results suggest that nicotine improves the retention of the information when administered either before or just after the acquisition, or before the restitution of the information. These effects were not associated with a

Acknowledgments

During the course of this investigation, C. Puma was supported by a grant from the Société Française de Tabacologie, and O. Deschaux was supported by a grant from the DRET/CNRS.

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