Periodic maternal separation of neonatal rats produces region- and gender-specific effects on biogenic amine content in postmortem adult brain

Early environment exerts profound effects on mammalian behavioral and neural development. The aim of this study was to describe changes in adult neurochemistry in the rat following repeated neonatal maternal separation (RMS) during the preweaning period, a procedure known to induce enduring behavioral effects. Following RMS, rats show an attenuated locomotor response to novelty, to D-amphetamine, and attenuated behavioral responses for conditioned incentives as adults. These behavioral effects are broadly opposite in direction to those found following postweaning isolation rearing. Isolation rearing-induced behavioral changes are associated with profound changes in central monoamine function. Following RMS, adult rats had increased tissue levels of dopamine in both dorsal and ventral striatum. The turnover of dopamine, as determined by the ratio of DOPAC to dopamine, was decreased in the mPFC of RMS subjects. Serotonin levels were reduced in dorsal hippocampus of RMS rats of both sexes and in the mPFC of male RMS rats. Noradrenaline levels were increased in the dorsal hippocampus in female, but not in male, RMS rats. These data provide evidence that, in addition to the adult behavioral consequences, RMS leads to profound, region-, and gender-specific changes in brain monoamine content. The developmental specificity of these results is discussed with respect to their possible role in altered behavioral development and psychopathology.