Marijana Peruzović

Differential Effect of Pre- and Postnatal Litter Size Reduction on Body Weight and Development of Stress Response in the Rat

The postnatal development of pups belonging to the small, prenatally reduced litters (PRN) was compared to that of pups of the postnatally reduced litters (PST) and to that of pups of intact, normal-size litters (CON). Body adrenal and pituitary weight gain as well as maturation of the pituitary-adrenal system were enhanced in the PRN and PST pups as compared to the CON pups in the 3 postnatal weeks. However, significant differences in some data between the PRN and PST pups were found, indicating the more pronounced beneficial effect of the prenatal reduction of litter size. The postnatal litter size reduction abolished the weight gain of the testes. The prenatal reduction of litter size resulted in a similar, although less pronounced negative effect.

Behavioral characteristics of the offspring of adolescent rats

The aim of this study was to test the hypothesis that, during adulthood, the offspring of adolescent rats differ in emotionality, learning and memory from the offspring of adult rats. The behavior of the offspring of adolescent (age, 50-55 days) and adult rats (age, 90-95 days) was tested in the open field, activity cage, and passive and active avoidance apparatus. The latencies during training and testing in the passive avoidance apparatus of the offspring of adolescent parents were shorter than the latencies of control offspring (P<0.001 on both training and testing days). Offspring of adolescent parents showed shorter latency time in acquisition trials during active avoidance testing compared to control offspring (P<0.001). They also showed a higher number of active avoidance responses in the last four blocks of acquisition (P<0.001) and first two blocks of extinction trials (P<0.05 and P<0.001, respectively). The offspring of adolescent parents showed higher latency on the first day of testing in the open field (P<0.01) and a lower latency on the third day of testing (P<0.01). They also showed higher activity during all three days of testing (1st and 2nd day: P<0.01; 3rd day: P<0.05). The spontaneous activity of the offspring of adolescent parents in the activity cage was higher in the last three intervals of testing (P<0.001). In summary, the offspring of adolescent parents were less anxious and tended to be more active. The results of two learning and memory tests were opposite, but could be explained by a higher exploratory drive of the offspring of adolescent parents. This was probably due to chronic malnutrition stress and the disturbed mother-infant relationship in the litters of adolescent mothers.

Significance of the Biphasic Developmental Pattern of the Hypothalamo-Pituitary-Adrenocortical System in the Rat

One group of neonatal rats was injected with metopirone at 2-5 days and the second group at 7-10 days of age. At 14 and 21 days all rats treated with metopirone had reduced body and adrenal weights in comparison with their saline-treated littermates. At 21 days the smallest adrenals were in the rats treated with metopirone at 7-10 days. Metopirone increased resting and stress levels of adrenal and plasma corticosterone in the 14-day-old rats and the response to stress by the adrenal corticosterone increase in the 21-day-old rats. The differential effect of metopirone applied in two developmental periods was indicated.

Pituitary and Adrenal Glands in Neonatal Rats Studied by Metopirone (Su4885)

One half of each litter of the 2- and 7-day-old rats was injected twice daily for 3 consecutive days with 15 mg/100 g body weight of metopirone (MET) in 0.05 ml of saline, and the remaining littermates with saline only. At the ages of 5 and 10 days, one half of the pups was sacrificed immediately, and the second half 20 min after s.c. injection of histamine as a stressor. MET depressed body weight and induced adrenal hypertrophy in the 5- and 10- day-old rats, and pituitary hypertrophy in the 5-day-old rats only. In resting condition the adrenal glands of the 5-day-old rats treated with MET contained less corticosterone (determined fluorometrically) than the 5-day-old control and the 10-day-old pups treated also with MET. Furthermore, neonatal MET treatment induced (histamine) stress response by the increase in adrenal corticosterone content in the 10-day-old rats, and by the increase in corticosterone content in plasma in both ages. The results indicate high sensitivity of the young neonatal rats to hormonal manipulations. They also yield additional support to the concept of functional integrity of the hypothalamo-pituitary-adrenocortical system in neonatal rats, and to the flexibility of the postnatal developmental pattern of stress response.

Long-term effects of naturally occurring within-litter differences in body weight of rats

From 10 litters of intact Fischer rats, three groups of each sex were formed on the basis of body weight at 30 days of age: Light (L), Medium and Heavy (H). Their weights were examined again at 60, 90, and 120 days. At 60 days the M animals had caught up with the H group, leaving behind the L animals which remained lighter at the end of the experiment. Starting at 63 days, the animals were given several behavioral tests. Behavioral differences between M and H groups existed at the age when weight differences between them had disappeared. The results indicate the longlasting effect of naturally occurring within-litter differences in body weight and behavior. The procedure used may help in studies of longlasting effects of early feeding.

An in vitro study of sex hormone metabolism in the pituitaries and gonads of neonatal and young rats: the effect of prenatal reduction of litter size

Through incubation with radioactive substrates, the in vitro activity of 17β-dehydrogenase (17-DHG) was studied in the testes of male and the pituitaries of both sexes of rats from birth to the 50th day of life, and the activity of 20 α-dehydrogenase (20-DHG) was studied in the ovaries of developing female rats and in females at parturition. Furthermore, the activities of 5 α-reductase (5-RT) in testes, ovaries and pituitaries were included in the study. The results obtained in rats belonging to litters of normal size (NL: 8–10 pups) were compared to those of small, prenatally reduced litters (RL: 2–5 pups). In both groups a biphasic developmental pattern of testicular 17-DHG activity was found. Maximal activity occurred immediately after birth, and minimal on the 21st postnatal day. In contrast, the activity of testicular 5-RT was low at birth and increased constantly towards the 50th day. Both enzymes were more active in the testes of the RL than in those of the NL rats early neonatally. 20-DHG was inhibited at birth in both NL and RL offspring ovaries. The peak of ovarian activity occured on the 14th day. The ovarian 5-RT activity displayed similar developmental pattern although with higher values. 17-DHG and 5-RT were more active in the pituitaries of the neonatal females than of the males. The male RL rats had smaller 17-DHG pituitary activity than the NL rats in the first three postnatal weeks, whereas the activity of 5-RT immediately after birth was more active in the pituitaries of the NL than in those of the RL females. The difference disappeared shortly after birth.