Age differences in the impact of forced swimming test on serotonin transporter levels in lateral septum and dorsal raphe

Rosa-Elena Ulloa,Lucía Martínez-Mota,Aliyeri Díaz-Valderrama,Martha León-Olea,Jaime Herrera-Pérez

doi:10.1186/1744-9081-10-3

Abstract

BackgroundForced swimming test (FST) is an animal model which evaluates behavioral despair and the effect of antidepressants such as the selective serotonin reuptake inhibitors; the FST modifies the expression of some receptors related to antidepressant response, but it is not known whether serotonin transporter (SERT), their main target, is affected by this test in animals of different ages. Antidepressant response has shown age-dependent variations which could be associated with SERT expression. The aim of the present study was to analyze changes in the SERT immunoreactivity (SERT-IR) in dorsal raphe and lateral septum of male rats from different age groups with or without behavioral despair induced by their exposure to the FST, since these two structures are related to the expression of this behavior.MethodsPrepubertal (24 PN), pubertal (40 PN), young adult (3–5 months) and middle-aged (12 months) male rats were assigned to a control group (non-FST) or depressed group (FST, two sessions separated by 24 h). Changes in SERT-IR in dorsal raphe and lateral septum were determined with immunofluorescence.ResultsPubertal and middle-aged rats showed higher levels of immobility behavior compared to prepubertal rats on the FST. SERT-IR showed an age-dependent increase followed by a moderate decrease in middle-aged rats in both structures; a decreased in SERT-IR in lateral septum and dorsal raphe of pubertal rats was observed after the FST.ConclusionsAge differences were observed in the SERT-IR of structures related to behavioral despair; SERT expression was modified by the FST in lateral septum and dorsal raphe of pubertal rats.

Highlights

Forced swimming test (FST) is an animal model which evaluates behavioral despair and the effect of antidepressants such as the selective serotonin reuptake inhibitors; the FST modifies the expression of some receptors related to antidepressant response, but it is not known whether serotonin transporter (SERT), their main target, is affected by this test in animals of different ages
Serotonin transporter (SERT) is responsible for terminating the serotonin (5-HT) action in the extracellular space by its reuptake into presynaptic terminal, controlling the availability of this neurotransmitter in the synaptic cleft [1]. This protein is the main target of the selective serotonin reuptake inhibitors (SSRIs), which bind SERT blocking its activity; this action allows an increase in 5-HT levels in the synaptic cleft and in serotonergic neurotransmission, being this first step for the antidepressants’ long-term effect [2,3]
Animals Male Wistar rats from the vivarium of the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz were housed 4–8 per cage in polycarbonate boxes according to age on an inverted 12-h light/dark schedule in a temperature-controlled (22°C) room

Summary

Introduction

Forced swimming test (FST) is an animal model which evaluates behavioral despair and the effect of antidepressants such as the selective serotonin reuptake inhibitors; the FST modifies the expression of some receptors related to antidepressant response, but it is not known whether serotonin transporter (SERT), their main target, is affected by this test in animals of different ages. Serotonin transporter (SERT) is responsible for terminating the serotonin (5-HT) action in the extracellular space by its reuptake into presynaptic terminal, controlling the availability of this neurotransmitter in the synaptic cleft [1] This protein is the main target of the selective serotonin reuptake inhibitors (SSRIs), which bind SERT blocking its activity; this action allows an increase in 5-HT levels in the synaptic cleft and in serotonergic neurotransmission, being this first step for the antidepressants’ long-term effect [2,3]. In rats mRNA for SERT can be determined by embryonic day 13, and the uptake of 5-HT reaches adult levels at birth in brain synaptosomes, at five weeks of age the amount of uptake is doubled and decreases to adult levels again [6] Specific areas, such as the median raphe exhibit a 25% decrease of SERT density in adults compared to prepubertal rats [7]. SERT binding in 3 to 18 years old children and adolescents shows an increase [8], followed by a decrease at the approximate rate of 10 percent per decade [9]

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