Effect of neonatal hydrocortisone treatment on brain monoamines in developing rats.

Abstract

Abstract-In our previous study, neonatal treatment with hydrocortisone was shown to produce a marked retardation of pituitary-adrenocortical development in infant rats. The present investigation was an attempt to determine whether or not the retarded activity is caused by functional changes in brain monoamine systems. In rats treated with hydrocortisone (0.5 mg/rat, s.c.) on the 2nd day of life, the development of whole brain was suppressed significantly. However, norepinephrine, dopamine and serotonin contents in the brain were higher in these rats than in controls. These changes of mono amine contents were apparent in the hypothalamus, diencephalon and pons-medulla oblongata.Our data suggest that monoaminergic nervous systems are potentiated with hydrocortisone in these brain regions, although the results do not necessarily explain the retarded hypothalamo-pituitary function.Neonatal treatment of rats with several corticosteroids caused a marked atrophy of the adrenal gland and the thymus, these producing the wasting syndrome (1). In the treated animals, circadian rhythm of plasma corticosterone appeared at 4 weeks of age, but the plasma levels of corticosterone were significantly lower than those of controls until 6 weeks (2). Since the secretion of ACTH is likely to be affected by brain monoamines (3), the lowered plasma corticosterone levels in neonatally hydrocortisone-treated rats might be related to changes in monoamine contents in the brain. In this regard, Ulrich et al. (4) reported that both norepinephrine and serotonin in the medial hypothalamus were elevated, but dopamine levels did not increase in those rats at 30 days of age. However, these workers determined the content in the hypothalamus at one age only. More recently, Nyakas (5) found an increased norepinephrine content in the hindbrain of 4 month old rats given corticosterone on the 3rd to 5th postnatal days. The present study was undertaken to observe serial changes in monoamine contents from 1 to 7 weeks of age in the brain of rats given hydrocortisone neonatally. Our results are related to the ontogenic pattern of brain monoamines, as affected by hydrocortisone treatment. MATERIALS AND METHODSMale and female Wistar rats were housed at a constant temperature of 25±2'C under controlled lighting (fluorescent illumination from 07:00 to 19:00). Rat biscuits (Oriental Yeast Co.) and water were given ad lib.Newborn rats were given 0.5 mg hydrocortisone acetate (Merck) in 0.05 ml solvent s.c., on the 2nd day of life. The solvent consisted of 0.4 % polysorbate-80, 0.5 % carboxy methylcellulose and 0.5% benzylalcohol in 0.9% NaCI. Control rats were given the solvent only. About three-fourths of the litters were treated with hydrocortisone and the remaining served as controls. The rats were left with their mothers until weaning at 21 days of life.Almost 1,000 newborn rats were used, but more than 50 % of the infant rats given hydro cortisone died within 10 days.The animals were decapitated between 13:00 and 14:00 hr. The whole brain was quickly remov...

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