Maternal separation (MS) induces profound behavioral and neurochemical dysregulations in adult rodents. In the present longitudinal study, we investigated the effects of repeated (4h/day) maternal separation during postnatal days 1-21 on serotonergic synthesis and activity in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus of juvenile (post-natal day 21, PND 21), adolescent (PND 35) and early adult (PND 56) male Wistar rats. We found that MS increased 5-HT levels in the PFC of juvenile rats, and although MS increased 5-HT and 5-HIAA levels in the NAc of adolescent rats, the ratio between 5-HIAA and 5-HT decreased in the PFC. In addition, MS-treated adult rats showed increased levels of 5-HT in the PFC as well as 5-HT and 5-HIAA in the NAc. These data provided evidence that MS leads to profound and age-specific changes in serotonergic synthesis and activity in rodents. Our study also found that there are U-shaped and inverted U-shaped patterns for serotonergic synthesis and serotonergic activity from younger rats to adults, respectively. Together, our findings support the use of maternal separation as an animal model for studying the neurobiological pathogenesis of neurodevelopmental diseases.
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