Implication of 5-HT7 receptor in early-life stress modulation of developing prefrontal-raphe circuits in mice

WU, G; ARGAÑARAZ, CV; ADJIMANN, TS; SOIZA REILLY, M

CABA

Congreso; Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2022

SAN

Maternal separation (MS) stress during postnatal days 2 to 14 (P2-14) in mice produces depressive-like and anxiety phenotypes in the adult life. These changes are accompanied by enhanced connectivity of the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) synaptic circuit (PFC-DRN), a main pathway involved in stress-coping responses and mood control. Similar changes were found in mice treated with the antidepressant fluoxetine during the same period. In that model, activation of 5-HT7 receptors has been shown to mediate both the alterations on the PFC-DRN synaptic circuit and adult emotional responses. In this study, we investigated if the activity of the 5-HT7 receptors could also mediate the synaptic changes observed in the model of MS. To this aim, we exposed mice to MS during P2-14 while administering a selective 5-HT7 receptor antagonist (SB-269970, s.c. 20mg/kg/day). At P15 we analyzed the synaptic innervation of the PFC-DRN circuit with the high-resolution immunofluorescent technique array tomography in maternally-separated SB-269970-treated mice and their saline controls. Our study will help to determine if 5-HT7 receptors have a role in the early-life stress vulnerability of prefrontal circuits.