Best Dose

Overall Zero Short Medium Long Delay interval

FIGURE 8.4 Upper panel: The nicotine-induced change in overall (all four delay intervals combined) DMTS performance by aged male (filled circles) and female (open circles) rhesus monkeys plotted as a function of dose during sessions initiated 10 min after nicotine injection (not depicted: data derived from sessions run on the day after nicotine injection). For males, there was a significant overall treatment (nicotine) effect, F(2,10) = 11.8, P=0.002), but there was no significant interaction between treatment and dose, F(6,29) = 0.55, P = 0.76. For females, there was no significant overall treatment effect, F(3,18) = 2.46, P = 0.096 and no significant interaction between treatment and drug, F(6,36) = 0.83, P = 0.55. Also, the male subjects exhibited a significantly greater response to nicotine than did the females, F(1,38) = 4.63, P = 0.0378. Lower panel: The nicotine-induced change in DMTS performance by aged male and female rhesus monkeys plotted as a function of delay interval. The data are presented as the average best dose for each group. The best dose was determined for each subject as that dose which provided the greatest overall response (all delays averaged) to nicotine. The data are derived from sessions initiated 10 min after nicotine injection (not depicted: data derived from sessions run on the day after nicotine injection). In males and females, nicotine improved task performance overall, F(2,10) = 12.8, P = 0.002, and F(2,12) = 10.7, P = 0.002, respectively, but there were no significant interactions between treatment effect and delay for either group (P>0.80).

Alternatively, the differential response to the cognitive enhancing properties to nicotine observed in females may suggest accelerated neural deterioration with developing loss of responsiveness to drug therapy.

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