Dysregulation in NPY expression and feeding behavior in adolescent rats by neonatal maternal separation.

Abstract

Sprague-Dawley pups were separated from dam for 3 h daily (MS) during PND 1–14, or left undisturbed (NH). Male pups were subjected to repeated fasting/refeeding schedule from PND 28; i.e. deprived from food, but not water, every other day and had free access to chow and water during the alternate days (MS/RF or NH/RF). MS/RF lost more weights by fasting, but gained more by refeeding, compared to NH/RF. Compensatory hyperphagia during refeeding days diminished gradually in NH/RF, but remained significant in MS/RF. Pups in NH/RF and MS/RF were sacrificed on PND 29 after the first fasting, or PND 40 satiated and PND 41 fasted. Hypothalamic NPY, CRH and plasma corticosterone, leptin were compared with age-matching free-fed controls (MS/C or NH/C). On PND 29, the arcuate NPY mRNA was significantly increased by 24 h fasting in NH, but not in MS. The PVN-CRH decrease and corticosterone increase upon fasting were bigger in MS than in NH. Basal leptin level increased in MS compared with NH, although no difference was found in fat mass. After repeated fasting trials, the arcuate NPY expression responding to fasting was significant in MS, but not in NH, suggesting an implication in persistent hyperphagia in MS/RF, but not in NH/RF. The elevation of corticosterone and the decrease of PVN-CRH upon fasting still remained bigger in MS than in NH. The results suggest that neonatal maternal separation may enhance the HPA axis activity, lead to dysregulation of the arcuate NPY expression and feeding behavior in adolescent rats.