Multiple early alterations in developing prefrontal‐raphe circuits by postnatal exposure to SSRI antidepressants in mice

ADJIMANN, TS; FERNANDEZ, SP; BARIK, J.; SOIZA REILLY M

CABA

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

SAN

Early-life exposureto antidepressant drugs acting as selective serotonin reuptake inhibitors(SSRIs), like fluoxetine, has long-lasting detrimental consequences inprefrontal circuits crucially engaged in stress-coping and mood control. Thus,mice treated with fluoxetine during a postnatal critical period (P2 to P14)show alterations in the connectivity of the prefrontal cortex to dorsal raphenucleus (PFC-to-DRN) circuit, accompanied by increases in depressive-like andanxiety behaviors in adult life. In this study, we investigated the short-termeffects (at P15) of fluoxetine exposure in the critical period on the synapticconnectivity of the developing PFC-to-DRN circuit, and whether this couldaffect the response of DRN serotonin neurons to stress. Our quantitativeanalysis using a high-resolution microscopy technique (array tomography) showeda synaptic hyper-innervation of the developing PFC-to-DRN circuit influoxetine-exposed mice in comparison to controls. These changes in PFCafferents were detected onto both serotonin and non-serotonin neurons of theDRN. Additionally, early fluoxetine exposure topographically dampened theactivation of DRN serotonin neurons in response to an acute stress (forcedswim), as revealed by c-Fos immunohistochemistry. These findings indicate thatearly-life exposure to SSRIs alters the ontogenetic trajectory of thePFC-to-DRN synaptic circuit, likely contributing to adult emotionalalterations.@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;}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:EN-US;}.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:EN-US;}.MsoPapDefault{mso-style-type:export-only;line-height:115%;}div.WordSection1{page:WordSection1;}