The high levels of melatonin in the daytime associated with a lack of response to light exposure in AD patients may be due to the neurodegenerative process of this disease.

1 We destroyed dentate granule cells unilaterally or bilaterally by means of intrahippocampal injection of colchicine in rats. Subsequently, we observed behavioural changes following the intraperitoneal injection of 2 mg kg 71 methamphetamine or saline, in addition to quantitatively assessing Fos protein expression in several brain regions, including the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus accumbens. 2 Bilaterally lesioned animals, when administered saline, showed a marked increase in locomotor activity compared with those of non-lesioned animals. With respect to the methamphetamine response, bilateral destruction resulted in a marked enhancement of locomotor activity, while the unilateral destruction led to a marked increase in rotation predominantly contralateral to the lesioned side, with no identi®able change in locomotor activity. 3 Bilaterally lesioned animals, when administered saline and having undergone an immunohistological examination, showed a marked increase in Fos expression in both sides of the nucleus accumbens. Bilaterally lesioned animals administered methamphetamine showed a marked increase in Fos expression in the right and left sides of all regions tested. Unilaterally lesioned animals administered methamphetamine showed a signi®cant and bilateral enhancement in Fos expression in the medial prefrontal and cingulate cortices, and a marked and unilateral (ipsilateral to the lesioned side) enhancement of Fos protein in the piriform cortex, dorsal striatum, and nucleus accumbens. 4 The present ®ndings suggest that dentate granule cells regulate methamphetamine-associated behavioural changes through the function of widespread areas of the brain, mostly the nucleus accumbens.

The daily profile of serum level of melatonin was studied in 10 young and 13 elderly subjects. All of the subjects were physically and psychiatrically healthy and did not have any clinical symptoms related to rhythm disturbance. Blood samples were taken every 3 h for 1 day and serum melatonin levels were determined by RIA. All except for 1 of the elderly subjects exhibited a clear circadian rhythm of serum melatonin level with a nocturnal peak. In both subject groups, the melatonin rhythm showed significant diurnal variation. There was no significant difference in the total melatonin level per day between young and elderly groups, suggesting that there was no influence of aging on daily total melatonin secretion. However, there was a marked difference in the features of the melatonin rhythm between the two groups, i.e., a rapid decline of the melatonin level from the nocturnal peak in the elderly group, suggesting that the off-set time of melatonin secretion advances with aging. Our findings suggest that the pattern of melatonin rhythm alters significantly without clear clinical symptoms in the process of senescence.

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