engleski

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

Serotonin (5-hydroxytryptamine, 5HT) is present both, in peripheral tissues where it regulates platelet aggregation and intestinal functions, and in the brain where it acts as a neurotransmitter and mediator of the perinatal development of 5HT neurons. Alterations in 5HT neurotransmission are indicated as biological substrates in several neuropsychiatric disorders, including autism. The most consistent 5HT-related finding in autism is elevated blood 5HT levels, while 5HT levels in brain were found to be decreased. It is assumed that high blood 5HT levels, resulting from the dysregulation of the peripheral 5HT-homeostasis, could reach the brain, before the formation of the blood-brain barrier, and inhibit development of 5HT neurons. In an attempt to explore the relationship between disturbed peripheral 5HT homeostasis and central 5HT functioning, three groups of Wistar rats were treated subcutaneously with either an immediate 5HT precursor 5-hydroxytryptophan (5HTP, 25 mg/kg), a non-selective MAO inhibitor tranylcypromine (TCP 2 mg/kg), or saline, during the period of most intensive development of 5HT neurons - from gestational day 13 to post-natal day (PND) 21. On PND 21 and PND 70, blood samples were collected from jugular veins under ether anesthesia. Animals were then decapitated and prefrontal cortices isolated from the brains. Peripheral 5HT concentrations were determined by ELISA and expressed per mL of blood. Brain 5HT concentrations were measured by high-performance liquid chromatography with electrochemical detection and expressed per mg of wet tissue. In the periphery, treatment with both compounds resulted in significantly elevated blood 5HT concentrations on PND 21, compared to saline treatment. At adult age, 5HT blood concentrations remained elevated only in TCP treated animals. In the brain, only TCP treatment induced significant 5HT elevations on PND 21. However, adult age animals from both experimental groups displayed significantly lower 5HT concentrations than the saline treated rats. The results indicate that: a) the treatment with the 5HT precursor induced a temporary disturbance in peripheral 5HT homeostasis that caused modest but permanent disturbance in central 5HT homeostasis, presumably acting through increased blood 5HT levels ; b) the treatment with the MAO inhibitor induced drastic and permanent 5HT dysregulation, both peripherally and centrally, presumably by reducing 5HT metabolism simultaneously in the brain and the periphery.

serotonin; autism; hyperserotonemia; blood serotonin levels; brain serotonin levels

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