The effects of perinatal treatment with serotonin synthesis precursor or serotonin degradation inhibitor on the serotonin homeostasis in adult rats

Blažević, Sofia Ana (2013) The effects of perinatal treatment with serotonin synthesis precursor or serotonin degradation inhibitor on the serotonin homeostasis in adult rats. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

Serotonin (5HT) regulates the development of its own neurons and target tissues during neurogenesis, therefore deviations from optimal 5HT concentrations during brain development can lead to structural and functional anomalies. In this thesis, through the chronic perinatal treatment with the immediate serotonin synthesis precursor, 5- hydroxytryptophan (5HTP, 25 mg/kg), or with an inhibitor of 5HT degradation, tranylcypromine (TCP, 2 mg/kg), we have increased 5HT concentrations in rats with the aim of investigating the effects on adult brain 5HT homeostasis. During the treatment 5HTP significantly increased 5HT levels in the peripheral compartment (hyperserotonemia), and TCP in the peripheral and central compartment. Both treatments had long-lasting/permanent consequences on the function of the central 5HT compartment, evident through changes in 5HT concentration and metabolism, expression of 5HT-regulating genes and serotonin related behavior. The fact that developmental disturbances in 5HT metabolism induced permanent disturbances in function of central 5HT compartment points to the genes that regulate 5HT metabolism as potential candidates for research in 5HT-related behavioral disorders. The effects of both treatments where analogous, showing a dose-effect: central 5HT homeostasis was mildly altered in animals with developmental disturbances only in peripheral 5HT homeostasis (5HTP), and drastically altered in animals with developmental disturbances in both central and peripheral 5HT homeostasis (TCP). These findings suggest that severe alterations in 5HT function observed in psychiatric diseases may be caused by developmental disbalance in the central 5HT compartment and speak in favor of the theory of hyperserotonemia as a marker, not a cause, of disturbances in central serotonin homeostasis.

Item Type: Thesis (Doctoral thesis)
Keywords: serotonin, 5-hydroxytryptophan, tranylcypromine, hyperserotonemia, perinatal treatmen
Supervisor: Hranilović, Dubravka
Date: 2013
Number of Pages: 92
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 11 Feb 2014 11:37
Last Modified: 22 Sep 2014 09:41
URI: http://digre.pmf.unizg.hr/id/eprint/408

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