engleski

Perinatal exposure to 5-hydroxytryptamine or tranylcypromine alters cortical development and anxiety-like behavior in rat pups

Serotonin (5-hydroxytryptamine, 5HT) is involved in the regulation of brain development and modulation of essential behaviors. Drugs targeting the 5HT system are employed in the treatment of affective and anxiety disorders, also during pregnancy. Although their possible developmental effects in mammals are yet unexplored, the monoamine oxidase inhibitor tranylcipromine (TCP) or the 5HT precursor 5- hydroxytryptamine (5HTP), sometimes replace the widely used and well-studied SSRIs. We report developmental disturbances, as reflected in barrel field (BF) formation and separation- induced ultrasonic vocalization (USV), in Wistar rat pups treated with 2 mg/kg of TCP or 25 mg/kg of 5HTP, from gestational day 12 until postnatal day (PND) 21. Both treatments reduced body mass and lowered survival rate in comparison to saline-treated pups. Nissl staining of serial tangential sections across the dorsolateral telencephalic wall displayed diffused barrels with poorly defined walls in TCP-treated pups, and well-defined but significantly smaller barrels in 5HTP-treated animals. USV measurements after separation from the litter, performed on PNDs 10, 13 and 16, revealed significant increase in number and duration of vocalization and significant decrease in vocalization latency and peak frequency in TCP-treated pups, and significant increase in the usage of multiple frequency sweep calls in 5HTP-treated pups. Our results indicate that perinatal treatment of rats with 5HTP, and especially with TCP, affect cortical development and anxiety-like behavior, suggesting a need for thorough examination of the potential effects of these antidepressant treatments on the developing human brain.

Serotonin ; Ultrasonic vocalization ; tranylcypromine ; 5-hydroxytryptamine ; anxiety like behaviour

nije evidentirano