engleski

The effect of perinatal treatments with 5-hydroxytryptophan and tranylcypromine on central 5HT concentrations and metabolism in adult rats

Serotonin (5HT) is a biologically active amine present in mammals in brain and peripheral tissues. Autism is a neurodevelopmental disorder in which 5HT homeostasis is disturbed both centrally and peripherally, but the relationship between the 5HT disturbances in the two compartments is not understood. In an attempt to explore the relationship between disturbed peripheral 5HT homeostasis and central 5HT functioning, we exposed a developing rat brain to increased 5HT concentrations, by the treatment of rats with subcutaneous injections of the immediate 5HT precursor 5-hydroxy-L-tryptophan (5HTP, 25 mg/kg), a non-selective MAO inhibitor tranylcypromine (TCP, 2 mg/kg), or saline, from gestational day 13 to post-natal day 21. 5HTP significantly raised only peripheral 5HT concentrations, while TCP induced significant 5HT elevations in both compartments. The effects of the mentioned treatments on central 5HT levels and metabolism were then studied in adult rats. Cortical and midbrain 5HT, tryptophan and 5-hydroxyindol acetic acid concentrations were determined by HPLC in twelve 5HTP-, eight TCP-, and ten saline-treated rats. In 5HTP treated animals, modest decrease in 5HT concentration without effects on 5HT metabolism was observed in cortex, presumably due to hyperserotonemia-induced loss of 5HT terminals during brain development. In TCP treated rats, altered 5HT metabolism with strong decrease in 5HT concentrations was observed both in cortex and midbrain. We suppose that the inhibition of one 5HT-regulating element induced compensatory changes in the expression/activity of other 5HT-regulating elements leading to a permanently disturbed 5HT homeostasis in rats treated with MAO inhibitor.

serotonin; 5HT metabolism; HPLC; brain; 5-hydroxytryptamine; tranylcypromine; rats

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