Single-prolonged stress induces apoptosis in dorsal raphe nucleus in the rat model of posttraumatic stress disorder

IntroductionPosttraumatic stress disorder (PTSD) is characterized mainly by symptoms of reexperiencing, avoidance and hyperarousal as a consequence of catastrophic and traumatic events that are distinguished from ordinary stressful life events. Single-prolonged stress (SPS) is an established animal model for post-traumatic stress disorder (PTSD). The dorsal raphe nucleus (DR)-serotonin (5-HT) system is dramatically affected by swim stress and has been implicated in affective disorders. The 5-HT1A receptor (5-HT1AR) is critically involved in regulating mood and anxiety levels.ObjectiveIn this study, we investigated changes in the expression of 5-HT1AR in DR of rats after SPS which may reveal part of the pathogenesis of PTSD.MethodsRats were randomly divided into 24h, 4d and 7d groups after SPS and a normal control group, 5-HT1AR expression in DR was examined using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction.ResultsThe expression of 5-HT1AR in DR after SPS exposure was increased when compared to that in the control group (P < 0.05).ConclusionThese findings suggest increase of 5-HT1AR in DR of SPS rats, which may play important roles in the pathogenesis of PTSD rats.

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Light stimulation into dorsal raphe nucleus contributes to antidepressant effect for a stressed rat model

10.1101/821421 ◽

2019 ◽

Author(s):

Xiaotao Li

Keyword(s):

Rat Model ◽

Dorsal Raphe Nucleus ◽

Bright Light ◽

Light Therapy ◽

Dorsal Raphe ◽

Raphe Nucleus ◽

Antidepressant Effect ◽

Seasonal Depression ◽

Dorsal Raphé ◽

Effect Of Light

AbstractBackgroundLight therapy is frequently demonstrated by clinical trials to be effective to seasonal or non-seasonal major depression. However, the pathway underlying the light effect on mood remains unclear. Since a retino-raphe pathway was previously indicated to modulate 5-HT production, we hypothesize that the retinal projection into dorsal raphe nucleus (DRN) may play an important role in the light therapy for depression.MethodsA rat model of 14-day corticosterone administration (40 mg/kg/day subcutaneous injection) was mainly used to test the effect of light therapy on non-seasonal depressant-like behavior, and the involved neural circuitry and neurochemistry as well.ResultsBehavior results revealed that the bright light therapy especially with the blue light of 470 nm and 400 lux, effectively reversed the depression-like responses in those stressed rats. After elimination of retino-raphe projection using immunotoxin (Saporin) the effect of light therapy was significantly attenuated. Whereas activation of retino-raphe projection using HM3q chemogenetics was shown an effect similar to fluoxetine treatment. Furthermore, 5-HT3A positive GABA cells in the DRN were activated with high c-Fos expression that involved in an inhibition of 5-HT synthesis and a subsequent depressive behavior. While light therapy through retino-raphe projection deactivated the hyperaction of those GABA cells in the DRN; that eventually contributed to the antidepressant effect from light therapy.ConclusionsOur results indicate that the retino-raphe circuitry engaged antidepressant effect in DRN that contributed to the light therapy to the non-seasonal depression. 5-HT3A positive GABA cells in DRN was indicated to mediate this function of retino-raphe projection.

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