Effects of nicotinic agonists and antagonists on spatial working memory in normal adult and aged rats

Abstract

The present study had t w o goals (1) t o examine the effects of treatments with nicotinic agonist (nicotine) and antagonist (mecamylamine) on working memory in normal adult rats (14 months o f age), and (2) t o determine if treating aged (36 t o 42 months o f age), memoryimpaired rats with nicotine could improve their memory function. Memory testing was carried out using a delayed non-matching to position paradigm in a T-maze. Rats were trained t o run down one arm of the maze (e.g., right) on an information run and then, after a variable memory delay period of 10,90, or 180 sec, run down the other arm (e.g., left). In normal adult rats after water injection, memory accuracy was inversely related to memory delay (> 90, 75, and 67% accuracy at the 10,90, and 180 sec delays, respectively). Administration o f nicotine (0.1 or 0.4 mgikg), or mecamylamine (2.5 or 5 mg/kg), or combinations of these drugs had no significant effects on memory in these rats. However, mecamylamine alone or in combination with nicotine reduced running speed in the T-maze in normal adults, indicating that the drugs did produce some behavioral effects. In aged rats, memory accuracy after water injection was much lower than that of younger adults, averaging 64, 57, and 50% at 10, 90, and 180 sec delays. Interestingly, nicotine injections of 0.1 o r 0.4 mg/kg resulted in highly significantly improved accuracy in the memory task. The deficit in memory accuracy in aged rats, evident even at the shortest delay period (10 sec), suggests that the rats may have had impairments in attention o r visual discriminatory ability. If this is so, then the beneficial effects of nicotine observed in this study may be more related to its effects on attention rather than memory directly. o

Acute Nicotine Administration in Alzheimer’s Disease: An Exploratory EEG Study

“…Nicotine administration has been shown to improve the deteriorating memory of aged rodents and monkeys [24,25], and nicotine has also been found effective in attenuating cognitive deficits in animal models designed to mimic some of the cholinergic deficiencies observed in DAT [26]. Both smoking and nicotine have been shown to exert cognitive-enhancing effects in normal adults [27,28].…”

Smoking History and Aging-Associated Cognitive Decline:An Event-Related Brain Potential Study

“…Behaviorally, nicotine administration has been shown to improve the deteriorating memory of aged rodents and monkeys [14,15] and nicotine has also been found effective in attenuating cognitive deficits in animal models mimicking cholinergic deficiencies observed in DAT [16]. Both smoking and nicotine administration has been shown to exert cognitive enhancing effects in normal adult smokers [17][18][19] and nonsmokers [20,21] and, acute nicotine administration, although highly variable in its effects, has been reported to improve attention, information processing and psychomotor/vigilance functions in DAT patients [22][23][24][25].…”

Adult Ontogeny of Rat Working Memory of Social Interactions

“…Only in experimental paradigms that require learning or recalling tasks of imposing difficulty is there unequivocal evidence of limits imposed on cognitive abilities by age (8)(9)(10)(11). Tasks used to compare old and young animals often are of questionable ecological validity and require complex motor coordination for optimum performance (12)(13)(14). It is not surprising that an old rat may prove less proficient than a young animal at swimming in search of a hidden platform or at locating areward in a multiple "hole board" (13,15,16).…”