A Practical Approach, Second Edition=Ronald D. Ho.pdf

1124 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONHumansIn humans, the periodicity of wakefulness and sleep is observed by between 10-11 weeks of age(de Roquefeuil et al., 1993; Hellbrügge, 1960). Between the ages of 18 to 21 weeks, the longestduration of sleep occurred between 11 pm and 5 am (Kleitman and Engelmann, 1953) (Moore andUcko, 1957). De Roquefeuil et al. (de Roquefeuil et al., 1993) examined the sleep-wake rhythmsof 12 children admitted to a day-care at 4-5 months of age until approximately 15 months of age.The circadian rhythm of wakefulness and sleep is well established by 4 months of age. In this samestudy, the results indicated that at 7, 11 and 15 months of age the number of sleep spans continuedto decrease in a 24-hr period (4, 3 and 2, respectively), and the duration of an individual sleep spanprogressively increased (200, 210 and 260 minutes, respectively).RatsUp until PND12, nursing and burrowing for preferred sleeping and nursing positions are thedominant activities in rats (Bolles and Woods, 1964). Any movement by one pup is likely to disturbthe entire litter. Gradually after PND 12, activities such as exploring and grooming occur withincreasing frequency. By PND 15, some rats prefer to bury their heads under the litter to sleepwhile others prefer to climb on top. By PND 19, sleeping becomes quieter with less twitching andmoving around. By PND 27, an individual rat can sleep soundly while littermates are playing ontop of him. Interestingly during the first 3 weeks of life, rat pups do not exhibit the normal diurnalsleep cycle of adult animals, i.e., sleep during daylight, and activity at night (Bolles and Woods,1964). Alföldi et al. (Alföldi et al., 1990) demonstrated that by PND 23 waking activities predominatedduring the 12-h dark period.DogsThe development of electrocortical activity as measured by EEG in the dog has been well describedby Fox (Fox, 1971). The results of the EEG analysis indicated changes in behavioral state (e.g.,sleep, alertness) were not accompanied by significant changes in the EEG during the first twoweeks of life. Up until 7 days of age, sleep in the puppy consisted of mainly body jerks and twitchesincluding occasional vocalizations, sucking, crawling and scratching movements (which couldeasily be mistaken for an alert state). After the second week of life, slow-wave activity began toemerge and was associated with the development of quiet sleep. Three weeks of age marks atransitional point when the relative durations of wakefulness (or attentiveness) and activated sleepare similar, and the duration of quiet sleep is increasing. The onset of the mature EEG occursbetween 3 and 4 weeks of age, which also marks a critical period of socialization (Scott, 1962).By 4-5 weeks of age, the EEG has developed the full range of activity that is present in the adult.Non-Human PrimatesInfant monkeys have a less well-defined sleep/wake pattern than adult animals. By 2 to 8 days ofage, neonatal monkeys already tend to sleep more frequently at night than during the day (Bowmanet al., 1970).Conclusions for Sleep-Wake Cycle DevelopmentWhile development of adult-like sleep-wake cycles occurs postnatally, utilizing sleep-wake cyclesas a measure in juvenile toxicity studies will provide limited insight because its development isnot well understood.© 2006 by Taylor & Francis Group, LLC