SUPPRESSION OF MELATONIN BY LIGHT AND NIMODIPINE

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It is estimated that approximately 50% of Americans over the age of 65 have sleep disturbances. Sleep disruption and nocturnal wandering is the second most common problem which precipitates nursing home institutionalization, and with the aging of the American population, it is expected that the number of elderly who require nursing home care will increase dramatically over the next decade. Our long term goal is to understand the basis of and develop effective therapies for chronic sleep disturbances in older adults. Research in both humans and animals has suggested that age-related changes in the endogenous circadian pacemaker, combined with reduced exposure to light during the day, contribute to disruptions of sleep/wake rhythms in the elderly. Timed exposure to bright light can improve sleep efficiency and daytime performance in older adults. However, recent results in animal models of aging suggest that the effectiveness of light therapy for the treatment of sleep disorders may be limited by reduced responsiveness of the aging clock to light. In addition, animal studies indicate that the reduction in responsiveness to light by the aging pacemaker may be due to impaired regulation of calcium homeostasis. Treatments that decrease intracellular calcium levels, such as the calcium channel antagonist nimodipine, have been shown to exhibit neuroprotective effects, improve neural plasticity and reverse aging-associated declines in motor and cognitive performance. Recent results indicate that calcium channel antagonists can also increase the responsiveness of the clock to light, since nimodipine increases the magnitude of phase shifts of circadian activity rhythms following exposure to light in both young and old mice. The goal of this proposal is to test the hyposthesis that nimodipine will increase responsiveness of the human circadian system to light. This will be tested by assessing the effect of nimodipine on light-induced suppression of nocturnal melatonin levels. The results from this pilot study will provide the basis for a comprehensive study to determine whether nimodipine can enhance the effectiveness of light therapy for the treatment of sleep/wake disorders in the elderly.