ACUTE AND CHRONIC NICOTINE EFFECTS ON WORKING-MEMORY IN AGED RATS

Acute and chronic nicotine administration has been repeatedly been fou nd in our laboratory to improve working memory performance of normal a dult rats in the radial-arm maze. The current study was conducted to d etermine if acute or chronic nicotine administration would improve wor king memory performance in aged rats. Sixteen young adult (3-7 months) and 32 aged (24-28 months) male Sprague-Dawley rats were trained on a n eight-arm radial maze. A significant age-related choice deficit was seen during the 21 sessions of training. After training, half of the r ats in each age group were implanted with nicotine-containing osmotic minipumps and the other half implanted with vehicle-containing pumps. Consistent with previous work, the young adult rats given chronic nico tine (approximately 5 mg/kg per day as measured as nicotine base) show ed a significant improvement in working memory performance. In contras t, the aged rats did not show a significant effect of this dose of chr onic nicotine. After a 2 week withdrawal period the remaining rats und erwent a series of acute drug challenges with nicotinic and muscarinic agonists and antagonists as well as the dopaminergic antagonist halop eridol. Mecamylamine and haloperidol impaired the memory performance o f the young adult rats, whereas the aged rats showed no effect. In con trast, scopolamine impaired performance of both young adult and aged r ats in a similar manner. Both pilocarpine and nicotine improved the me mory performance of the aged rats, but did not improve the young adult rats, possibly due to a ceiling effect on performance. During the cho linergic agonist drug phase, the aged rats which had previously been g iven chronic nicotine infusions showed better performance than those w hich had not. The resistance of the aged rats to chronic nicotine-indu ced working memory improvements and acute mecamylamine-induced working memory deficits may have resulted from the decline in nicotinic recep tors seen with aging. Chronic co-administration of the nicotinic antag onist mecamylamine in a previous study was found to abolish the chroni c nicotine-induced working memory improvement. The aged rats were resi stant to haloperidol-induced deficits which may have resulted from the decrease in dopaminergic receptors seen with aging. Interestingly acu te cholinergic agonists including nicotine did improve working memory performance in the aged rats and previous chronic nicotine infusion wa s beneficial during the period of acute cholinergic agonist challenge. This suggests that nicotinic treatment may be of use for treating age associated memory impairments but that special dosing regimens may be required.