Experience of Neonatal Maternal Separation May Lead to a Long-term Modulation in the Neuronal Activity of Nucleus Accumbens in the Offspring

ABSTRACT

Dysfunction of the nucleus accumbens (NAcb) is implicated in the development of anhedonia, a core symptom of major depressive disorder. In order to define the neural basis of depression-like behaviors induced by experience of neonatal maternal separation (MS), both basal and stress-induced neuronal activations in the NAcb of adolescent rats with MS experience were examined parallel with palatable food intake. Rat pups were separated from dam daily for 180 min during the first two weeks of age (MS), and non-handled control (NH) pups were left undisturbed. After weaning on postnatal day (PND) 22, a half of NH or MS pups were subjected to 1 h of restraint stress every even day during PND 28~40 (NH/R or MS/R), and then had free choices of chow and chocolate cookie for 1 h immediately after returned to home cage. The rest half of NH and MS pups (NH/C or MS/C) received free choices of chow and cookie in the same time schedule with stress group, just omitting restraint stress. Cookie intake was significantly decreased in MS/C, whereas c-Fos expression in the NAcb and plasma corticosterone increased, compared to NH/C. Restraint stress suppressed cookie intake and increased the NAcb c-Fos expression in NH/R, but not in MS/R. The plasma corticosterone of NH/R, but not of MS/R, increased following repeated restraint stress. These results suggest that the increased neuronal activation in the NAcb of MS/C may be implicated in the development of anhedonia by MS experience, perhaps, in relation with a blunted responsivity of the hypothalamic-pituitary- adrenal axis to stress.