Differential improvement in memory-related task performance with nicotine by aged male and female rhesus monkeys

Central nicotine acetylcholine receptors have been targeted for the develop ment of novel treatments for memory deficits in Alzheimer's disease (AD) an d other neurodegenerative disorders. Nicotine itself has been shown to impr ove memory-related task performance in aged animals and in AD patients. Adm inistration of nicotinic receptor agonists to laboratory animals, and the e ffects of cigarette smoking in humans attributed to nicotine, have in many instances been shown to exert sexually dimorphic actions. Low doses (2.5-20 mu g/kg, intramuscularly) of nicotine have been shown to improve the perfo rmance of an automated delayed matching-to-sample (DMTS) task in aged rhesu s monkeys. The purpose of this study was to determine whether aged females receive the same level of benefit to the positive mnemonic action of nicoti ne as do males. In this study six male (21.7 +/- 1.2 years) and seven femal e (22.5 +/- 0.9 years) rhesus monkeys each received an ascending series of four doses of nicotine over 5 weeks. Most control parameters were similar b etween the two sexes, although task latencies were longer and more variable in the female subjects. The males maintained a significant improvement in task performance over the entire nicotine dose range. This level of improve ment extended to 24 h after nicotine administration. Task accuracy by femal es appeared to improve only after they received the two higher doses of nic otine, and their responses exhibited considerable variability over the enti re dose range. However, in calculating an individualized 'Best Dose', males and females exhibited a similar level of task improvement (15-30% above ba seline). Therefore, aged female subjects may require a greater level of ind ividualized treatment and perhaps higher doses of nicotinic agonists to ach ieve the maximal mnemonic benefit. (C) 1999 Lippincott Williams & Wilkins.