| First Author | Garcia-Garcia AL | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 5 | Pages | 1144-1156 |
| PubMed ID | 28147271 | Mgi Jnum | J:254253 |
| Mgi Id | MGI:6103475 | Doi | 10.1016/j.celrep.2017.01.021 |
| Citation | Garcia-Garcia AL, et al. (2017) Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors. Cell Rep 18(5):1144-1156 |
| abstractText | Lifelong homeostatic setpoints for mood-related behaviors emerge during adolescence. Serotonin (5-HT) plays an important role in refining the formation of brain circuits during sensitive developmental periods. In rodents, the role of 5-HT1A receptors in general and autoreceptors in particular has been characterized in anxiety. However, less is known about the role of 5-HT1A receptors in depression-related behavior. Here, we show that whole-life suppression of heteroreceptor expression results in a broad depression-like behavioral phenotype accompanied by physiological and cellular changes within medial prefrontal cortex-dorsal raphe proper (mPFC-DRN) circuitry. These changes include increased basal 5-HT in a mPFC that is hyporesponsive to stress and decreased basal 5-HT levels and firing rates in a DRN hyperactivated by the same stressor. Remarkably, loss of heteroreceptors in the PFC at adolescence is sufficient to recapitulate this depression-like behavioral syndrome. Our results suggest that targeting mPFC 5-HT1A heteroreceptors during adolescence in humans may have lifelong ramifications for depression and its treatment. |
