The effects of perinatal fluoxetine exposure on emotionality behaviours and cortical and hippocampal glutamatergic receptors in female Sprague-Dawley and Wistar-Kyoto rats

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Progress in Neuro-Psychopharmacology and Biological Psychiatry


Rationale: There is increasing concern regarding the use of selective serotonin reuptake inhibitors (SSRIs) in pregnancy. Animal studies repeatedly show increased anxiety- and depressive-like behaviours in offspring exposed perinatally to SSRIs, however much of this research is in male offspring. Objectives: The primary aim of this study was to investigate the effects of perinatal SSRI exposure on emotionality-related behaviours in female offspring and associated glutamatergic markers, in Sprague-Dawley (SD) rats and in the Wistar-Kyoto (WKY) rat model of depression. Secondly, we sought to investigate the glutamatergic profile of female WKY rats that may underlie their depressive- and anxiety-like phenotype. Methods: WKY and SD rat dams were treated with the SSRI, fluoxetine (FLX; 10 mg/kg/day), or vehicle, throughout gestation and lactation (5 weeks total). Female adolescent offspring underwent behaviour testing followed by quantitative immunoblot of glutamatergic markers in the prefrontal cortex and ventral hippocampus. Results: Naïve female WKY offspring displayed an anxiety-like and depressive-like phenotype as well as reductions in NMDA and AMPA receptor subunits and PSD-95 in both ventral hippocampus and prefrontal cortex, compared to SD controls. Perinatal FLX treatment increased anxiety-like and forced swim immobility behaviours in SD offspring but did not influence behaviour in female WKY offspring using these tests. Perinatal FLX exposure did not influence NMDA or AMPA receptor subunit expression in female WKY or SD offspring; it did however have restricted effects on group I mGluR expression in SD and WKY offspring and reduce the glutamatergic synaptic scaffold, PSD-95. Conclusion: These findings suggest female offspring of the WKY strain display deficits in glutamatergic markers which may be related to their depressive- and anxiety-like phenotype. While FLX exposed SD offspring displayed increases in anxiety-like and depressive-like behaviours, further studies are needed to assess the potential impact of developmental FLX exposure on the behavioural phenotype of female WKY rats.

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