Effects of neonatal handling on basal and stress-induced monoamine levels in the male and female rat brain

Abstract

Neonatal handling has pervasive effects on the rat brain leading to increased ability to cope with and adapt to stressful stimuli. We determined the effects of neonatal handling on the dopaminergic and serotonergic system, in the male and female rat brain, under basal conditions before and after puberty and after short- and long-term forced swimming stress. Exposure of animals to neonatal handling resulted in sex-dependent changes in the concentration and turnover of monoamines in the different brain areas. In the prepubertal brain, the effect of neonatal handling was manifested as an increase in dopamine turnover in the females, particularly in the hypothalamus, an increase in serotonin levels and a decrease in its turnover in all three brain regions examined of both males and females. Certain of the handling-induced effects observed in the prepubertal brain were reversed in the postpubertal animals. Thus, in the postpubertal brain, the handling-induced changes in serotonin levels and its turnover observed in both sexes before puberty were abolished. On the other hand, the handling-induced increase in hypothalamic dopamine turnover was maintained. After exposure to short-term stress, the effect of handling was manifested on one hand as decreased striatal dopamine levels in the females, and decreased dopamine turnover in the hypothalamus of both males and females, and on the other, as increased serotonin levels in the hypothalamus. After exposure to long-term stress, handled females had decreased dopamine turnover in the hypothalamus and the striatum, but there was no effect of handling on the serotonergic system. Our results provide some neurobiological evidence supporting the determinant role of the mother–infant relationship in the development of psychopathology. Neonatal handling, which modifies normal mother–pup interactions, results in alterations in brain dopaminergic and serotonergic systems, both of which are involved in the etiopathogenesis of major psychoses. Exposure to either short- or long-term stress in adult life results in sex-dependent changes in brain monoamines, which are affected by handling thus making coping more efficient and rendering the stressful stimulus less noxious.