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Perinatal Exposure of Rats to 5-Hydroxytryptophan Affects Midbrain Serotonin Homeostasis

Background: A considerable number of depressed women continue to use 5-hydroxytryptamine (5-HT) targeted antidepressants throughout pregnancy. The immediate 5-HT precursor, 5-hydroxytryptophan (5-HTP), is being increasingly offered as a natural and safer alternative to antidepressant medication. However, consequences of developmental exposure to increased 5-HTP concentrations on brain development and behaviour have not been studied in animal models or humans. During the perinatal period, 5- HT acts as a modulator of neural development. Growing evidence suggests the role of 5-HT, originating from the dorsal raphe nuclei (DRN), in the formation of the barrel field in the rodent somatosensory cortex. Topographically organized barrels, contained within the posteromedial barrel subfield (PMBS), represent the major facial whiskers, which rodents use to explore their environment.

Methods and Findings: We examined consequences of perinatal treatment of Wistar rats with 25 mg/kg 5-HTP, from gestational day 13 until postnatal day (PND) 21, on brain development. Compared to controls, 5-HTP treated rats displayed decreased birth-weight and postnatal weightgain. ELISA revealed increased serum but not cortical 5-HT concentrations at the end of treatment. Nissl staining of tangentially oriented serial sections across the dorsolateral telencephalic wall displayed unaffected cytoarchitecture of the PMBS, but significantly smaller barrel size on PND70, possibly leading to previously observed impairments in whisker-mediated perception. 5-HT immunostaining of the DRN region revealed significantly lower signal intensity in 5- HT positive cells, pointing to possible compensatory reduction of 5-HT content in DRN.

Conclusions: Our results suggest a need for examination of the potential neurological/behavioural effects in children prenatally exposed to 5-HTP.

Author(s): Sofia Ana Blazevic, Darija Soltic, Barbara Nikolic, Katarina Ilic, Natasa Jovanov Milosevic and Dubravka Hranilovic

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