Limits of learning enhancements with nicotine in old male rats
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Findings with young adult humans and animal models suggest that nicotine may serve both neuroprotective and cognition enhancing roles in old animals. A pair of experiments was conducted to examine drug-induced modification of the cholinergic nicotinic receptor subtype on rates of learning by young and aged rats. In experiment 1 males (4-7 months or 20-25 months old) were administered nicotine (0.0, 0.3 or 0.7 mg/ kg bwt SC injected daily) and tested in both a T-maze non-spatial discrimination paradigm and a hole board spatial task. Nicotine failed to improve acquisition by young animals on either task. Nicotine also failed to improve non-spatial learning by old animals. However, both dosages of nicotine improved performance by the old males in the spatial paradigm. In experiment 2, a 5-choice serial discrimination paradigm designed to better evaluate visual attention and spatial working memory in aging was used. Groups of old male rats were administered nicotine or mecamylamine (2 or 8mg/ kg), an antagonist of the nicotinic cholinergic receptor. Results were that the 0.3mg nicotine group learned the task fastest and achieved the highest learning asymptote. Both learning rates and final levels of performance were worst in the 8mg mecamylamine group. However, the 2mg mecamylamine rats were the equals of the control group and both reached a higher asymptote than the 0.7mg nicotine group. These data suggest that healthy old animals can accrue benefits from nicotinic activation but that the benefits are complex, being limited to certain dosages and to specific cognitive skills.
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Juergen Weiss, Center for Biomedicine, Univ. of Heidelberg, INF 347, D-69120 Heidelberg, Germany