Major Depressive Disorder (MDD) is a prevalent psychiatric disorder, affecting approximately 280 million people worldwide (WHO, 2023). Most research on depression has focused only on neurons. However, astrocytes respond to neurotransmitter release from nearby neurons by elevating internal calcium levels and subsequent release of neuroactive transmitters, including ATP, D-serine, and GABA. These substances can then modulate synaptic activity. Although serotonin (5-HT) has been hypothesized to play a role in the development and manifestation of depression for decades, the precise mechanisms that lead to MDD remain unclear. Since astrocytes express the 5-HT1A receptor, which is associated with depression, our study focuses on the influence of 5-HT1A receptor-mediated signaling in astrocytes within the medial prefrontal cortex (mPFC) on depressive-like symptoms in mice. In neurons, the 5-HT1A receptor (5-HT-R) is coupled to the Gi signaling pathway. Interestingly, in astrocytes, Gi-coupled receptors may cause internal calcium elevation. To verify this for the 5-HT1A-R, we performed calcium imaging in acute brain slices of the mouse mPFC. Activation of the 5-HT1A receptor resulted in a significant increase in calcium events in astrocytes. To manipulate the 5-HT1A-R pathway in astrocytes, we utilized our light-activatable 5-HT1A receptor chimera (Masseck et al. 2014). To study the social component of depression we performed the chronic social defeat test and activated the 5-HT1A receptor chimera during stress exposure on 10 consecutive days. Additionally, the chronic mild stress test was used to study anhedonia. Our data support the hypothesis that 5-HT1A-R mediated signaling in astrocytes influences depression and has an antidepressant effect.