Effect of the Neonatal Administration of a Single Dose of Chlorpromazine on the Subsequent Sexual Development of Male Mice

Abstract

A single injection of 20 \ g=m\ gchlorpromazine/g body weight given on Days 4, 6, 7, 8, 9 and 10 resulted in greater testis and seminal vesicle weight, and a general increase in spermatogenesis assessed at 30 days of age. A considerably greater effect was obtained when the injection was given on Day 7 compared with injection on any other day.The critical significance of the early postnatal period in mice and rats to subsequent sexual development is well established (Harris, 1964;Barraclough, 1966Barraclough, , 1968. Injection of female neonates with androgens results in suppres¬ sion of the phasic hypothalamic control of gonadotrophin secretion which is typical of the female and allows only the expression of a gonadotrophin secre¬ tion resembling that of the male. Up to 10 days of age in the rat (and approxi¬ mately the same time in mice: Barraclough & Leathern, 1954), the hypothalamus appears to be sensitive to androgens and in the presence of, for example, testosterone, will subsequently assume male characteristics.Treatment with the tranquillizer, chlorpromazine (Largactil), has been shown to impede the development of the male pattern of gonadotrophin control in rats if given during the first 10 days of life. Ladosky, Kesikowski & Gaziri (1970) have demonstrated that a single injection of 20 µg chlorpromazine (CPZ)/g body weight given to newborn male rats on Days 1, 5, 8, 12 or 15 post partum inhibited testicular development, as assessed by the proportion of semi¬ niferous tubules containing spermatids at 108 days of age. In contrast to this, injection of CPZ on Day 10 advanced the onset of spermatogenesis. The pro¬ portion of allografted ovaries showing luteinization 60 days after grafting was used as a measure of LH secretion : on this basis, LH secretion appeared to be stimulated by CPZ injection on Days 1, 5, 8 and 10. The peak of spermato¬ genesis in the animals injected on Day 10 coincided with a high proportion of luteinization in the allografted ovaries; otherwise, the correlation between the estimates of LH secretion and those of testis maturity was not good.The present investigation was designed to investigate further the effects of CPZ treatment during the early postnatal period on the subsequent develop¬ ment of testis maturity, using a different species, the mouse.Forty-four newborn mice of the LACA strain were injected subcutaneously 539

Growth, Metabolic and Adrenocortical Effects of Single and Repeated Administration of Diazepam in Piglets

“…1975;Dorner 1976). Neonatal administration of chlorpromazine to mice increased endocrine and spermatogenic function of the testes (Hogarth and Chalmers 1973). On the other hand, diazepam treatment of rats cancelled the majority of late androgenic effects of neonatal stress (Br d osova et al, 1975).…”