Developmental impact of SSRI antidepressants on emotional prefrontal circuits in mice

ARGAÑARAZ C; ADJIMANN T; SOIZA REILLY M

Congreso; XXXV Reunión Anual SAN2020; 2020

Sociedad Argentina de Investigación en Neurociencias

Early-life exposureto antidepressant drugs acting as selective serotonin reuptake inhibitors (SSRIs)like fluoxetine, has long-lasting detrimental consequences in prefrontalcircuits crucially engaged in stress-coping and mood control. Thus, micetreated with fluoxetine during a postnatal critical period (P2 to P14) show alterationsin the connectivity of the prefrontal cortex to dorsal raphe nucleus(PFC-to-DRN) circuit, accompanied by increases in depressive-like and anxietybehaviors in adult life. In this study, we investigated the short-term effects (atP15) of fluoxetine exposure in the critical period on the synaptic connectivityof the developing PFC-to-DRN circuit, and whether this could affect the responseof DRN serotonin neurons to stress. Our quantitative analysis using a high-resolutionmicroscopy technique (array tomography) showed a synaptic hyper-innervation ofthe developing PFC-to-DRN circuit in fluoxetine-exposed mice in comparison tocontrols. These changes in PFC afferents were detected onto both serotonin andnon-serotonin neurons of the DRN. Additionally, early fluoxetine exposure dampenedthe activation of DRN serotonin neurons in response to an acute stress (forcedswim), as revealed by c-Fos immunohistochemistry. These findings indicate that early-lifeexposure to SSRIs alters the ontogenetic trajectory of the PFC-to-DRN synapticcircuit, likely contributing to adult emotional alterations.<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Arial",sans-serif;mso-fareast-font-family:Arial;mso-ansi-language:#580A;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Arial",sans-serif;mso-ascii-font-family:Arial;mso-fareast-font-family:Arial;mso-hansi-font-family:Arial;mso-bidi-font-family:Arial;mso-ansi-language:#580A;}.MsoPapDefault{mso-style-type:export-only;line-height:115%;}size:612.0pt 792.0pt;margin:70.85pt 70.85pt 70.85pt 70.85pt;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}