Study of the intranasal administration of L-Tryptophan as a potential antidepressant treatment in a corticosterone-induced rat model for depression

Abstract

Depression is a prevalent mental health disorder characterized by depressed mood, anhedonia, and recurrent thoughts of death. It affects more than 280 million people worldwide and implies over 700,000 suicides annually. The disorder's etiology remains unknown, but certain hypotheses have been postulated to understand its possible pathogenesis. One of the most widely accepted is the monoaminergic hypothesis, characterized mainly by central deficiencies of monoaminergic neurotransmitters, such as serotonin (5-HT), dopamine (DA), and noradrenaline (NA). Today, the most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). However, they are not universally effective as it can take several weeks of daily dosing to appreciate their effects and they do not always work in all patients, resulting in treatment failure. This study aims to investigate the potential antidepressant properties of intranasally administered L-Tryptophan (L-Trp), the serotonin amino acid precursor, in a rat model of corticosterone-induced depression. Holding the hypothesis that L-Trp will increase serotonin levels in the brain promoting antidepressant behavior, several experiments such as microdialysis, behavioral tests, brain tissue analysis, and Western Blot technique were conducted. Results demonstrated that intranasal administration of L-Trp significantly increased serotonin levels in the prefrontal cortex of microdialysis rats. It also promoted a reduction of anxiety in the Open Field Test, and a reversed depressive behavior in the Forced Swimming Test. The prefrontal cortex, hippocampus, and midbrain also showed increased levels of monoamines in samples from treated rats. These findings exhibit potential antidepressant properties of the L-Trp that may offer a promising therapeutic approach to further discovering a new rapid-acting treatment for depression.