Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats

Abstract

The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, γ-aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats. Dopamine D2 receptor antagonist haloperidol was administered to the early postnatal TP-exposed PND21 and PND49 male rats 30 min prior to open field test. Haloperidol significantly ameliorated the motor behavioral and grooming behavioral defects induced by early postnatal TP exposure. The results demonstrated that early postnatal androgen exposure significantly disturbed the brain activity of developing male rats via enhancing the mesodopaminergic activity. It was suggested that abnormal increments of testosterone levels during the early postnatal development might be a potential risk factor for the incidence of some male-based childhood-onset neuropsychiatric disorders by affecting the mesodopaminergic system.