Early life stress and sex-specific sensitivity of the catecholaminergic systems in prefrontal and limbic regions of Octodon degus

Previous work in the precocious rodent Octodon degus has shown that exposure to early life stress (ELS) (induced by repeated parental separation) results in changes of excitatory, inhibitory and modulatory transmitter systems in prefrontal and limbic regions of the male brain. The aim of this study was to test the hypothesis that catecholaminergic fibers and dopamine transporters (DAT) are differentially vulnerable towards ELS-induced neuronal changes in male and female brains. The brains of adult male and female animals exposed to repeated early life stress (1 h/day separation from the family from P1 to P21) and control animals were compared and the densities of tyrosine hydroxylase (TH)-immunoreactive structures were quantified in prefrontal cortical regions. In the nucleus accumbens (NAc) and striatum, DAT-immunoreactivity as well as TH immunoreactivity was measured. Layer II of the prelimbic cortex displayed reduced TH-fiber densities in ELS males compared to control males; this effect was not seen in females. In contrast, layer V/VI of the lateral orbitofrontal cortex displayed elevated fiber densities in ELS males compared to controls; again this difference was not observed in females. The same trend was observed for layer III/IV of the ventral orbitofrontal cortex. No sex-specific effects in response to ELS were observed for DAT, whose density was elevated in the NAc of ELS males and females. These results are in line with our working hypothesis that ELS affects the development of catecholaminergic systems and we show here that ELS-induced differences of TH-immunoreactive fibers were more pronounced in male brains than in female brains.