S-22-5 - Intracerebral antisense oligonucleotides reduce mineralocorticoid-induced ingestive behaviors

Abstract

The endocrine response to stress is an important homoeostatic mechanism, and the secretion of glucocorticoids from the adrenal cortex is a central feature of this response. During early postnatal development, the neonatal rat displays a reduced hypothalamic-pituitary-adrenal (HPA) response to stress. This early period has been termed the ‘stress hyporesponsive period’ (SHRP). Maternal separation (Sep) of neonates from their mothers during early postnatal development alters the HPA response to stress. In this study, we report the effects of Sep during the SHRP. Female rats were time mated and randomly divided into control or Sep groups before birth. The Sep litters were removed from the mothers during the dark cycle for 6 h per day from postnatal day (PND) 2 to 10. On PND 28, the pups from both groups were weighed, the anogenital distance (AGD) was measured and the animals weaned. At 40 days of age, male and female animals from both groups were tested for open-field activity. As the animals matured, vaginal opening and estrous cycles were measured in females, and males were tested for male sexual behavior at adulthood. Basal, stress, and stress recovery serum corticosterone levels were measured from control and Sep male and female animals. Open-field activity was not significantly different between control or Sep male or female animals. Sep did not affect either vaginal opening or estrous cycles in female animals. Corticosterone secretion in response to stress was similar in control and Sep males and females; however, the recovery levels were significantly higher in Sep females than in Sep males or female control values. In male sexual behavior tests, Sep males had significantly longer mount latencies (time to the first mount), longer intromission latencies (time to the first intromission) and a significant reduction in the percent of animals ejaculating versus control values (controls 84 and Sep 50%). Therefore, Sep males as adults displayed altered reproductive behavior, whereas their stress recovery levels of corticosterone returned to near basal levels in a similar fashion to that observed for control non-handled males. In contrast, females displayed normal reproductive physiology, while their recovery levels of corticosterone remained high, unlike that observed with control females. Thus, significant gender differences in response to Sep (during the dark phase of the circadian cycle) were observed in the paradigm used in the present study.