Abstract:

Sleep has been shown to promote learning and memory, and reciprocally, sleep deprivation disrupts these cognitive processes. Moreover, evidence suggests that hippocampal cell proliferation (CP) and neurogenesis are closely tied to certain types of learning and memory. Previous animal studies have demonstrated that extended periods (? 48 h) of sleep deprivation suppress cell genesis in the hippocampus. As shorter periods of sleep loss are more relevant to the typical human experience, the present studies investigated the effects of short-term sleep disruption by physical and pharmacological stimuli on cell genesis in the rodent hippocampus.

In the present study of 14 hours of sleep deprivation by the gentle handling method, results suggested no overall change in the number of proliferating cells in the total DG. Regional decreases, however, were observed in the number of proliferating cells, thereby reflecting the general tendency for sleep deprivation to suppress hippocampal cell genesis, as reported by a number of other investigators.

The next studies investigated three stimulant drugs: caffeine, methamphetamine, and modafinil. Three administrations of these drugs over 14 hours exerted pronounced elevations in wakefulness when given during the normal sleeping period. While each of these drugs produced trends toward suppression of CP, the strongest decreases were observed during the light phase in animals treated with modafinil, the drug which most profoundly disrupted sleep. Regional variations in CP were observed in both caffeine- and modafinil-treated animals following administration during the resting period (light phase), but no such changes were detected during the active period (dark phase). These differences in the light vs. dark phases may reflect a role of sleep or other circadian-mediated factors in producing the regional changes in hippocampal cell proliferation following stimulant drug treatment.

These studies provide the first formal exploration into effects of caffeine and modafinil on adult hippocampal genesis, and extend existing methamphetamine studies. Importantly, they also provide insight regarding the influence of high doses of these drugs on disrupting sleep, and the implications of this drug-induced sleep disruption on hippocampal cell genesis and associated cognitive processes.