Intracisternal Administration of p-n-Octylphenol into Neonatal Rats Causes Hyperactivity Concomitantly with the Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End-Labelling (TUNEL)-Positive Cells in the Mesencephalon where Immunoreactivity for Tyrosine Hydroxylase is Reduced by the Chemical

Abstract

It is unknown which endocrine disruptors exert their effects on neuronal functions, particularly leading to behavioral alterations. To address this, we examined the effects of p-n-octylphenol, an endocrine disruptor, on rat behavior and cellular responses. Single intracisternal administration of p-n-octylphenol (87 nmol) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. The treated rats were about 1.5-fold more active in the nocturnal phase after administration of p-n-octylphenol than control rats. Immunohistochemical analyses revealed that p-n-octylphenol abolished immunoreactivity for tyrosine hydroxylase in the midbrain of 8 week-old rats, where terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL)-positive cells were also seen. Thus, this is the first demonstration that p-n-octylphenol certainly affected the developing brain, resulting in hyperactivity in the rat, most likely due to degeneration of mesencephalic tyrosine hydroxylase.