Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals

Abstract

Major depressive disorder (MDD) is among the most common mental disorders worldwide and is characterized by dysregulated reward processing associated with anhedonia. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD; however, their onset of action is delayed. Recent reports have shown that serotonin neurons in the dorsal raphe nucleus (DRN) are activated by rewards and play a vital role in reward processing. However, whether antidepressant treatment affects the DRN serotonin neuronal response to rewards in awake animals remains unknown. In this study, we measured the activity of DRN serotonin neurons in awake mice and determined the effects of antidepressants and chronic stress on DRN serotonin neuronal activity. We found that acute treatment with citalopram, an SSRI, significantly decreased sucrose-induced activation of DRN serotonin neurons. The decrease in response to acute citalopram treatment was attenuated by chronic citalopram treatment. Acute treatment with (S)-WAY100135, a 5-HTa 5-HT₁[A] receptor antagonist, dose-dependently inhibited the response to acute citalopram treatment. These results indicate that autoinhibition by activating 5-HT₁[A] receptors via acute SSRI treatment may blunt the reward response, which can be recovered after chronic SSRI treatment.