Perinatal exposure to fluoxetine increases anxiety- and depressive-like behaviours and alters glutamatergic markers in the prefrontal cortex and hippocampus of male adolescent rats: A comparison between Sprague-Dawley rats and the Wistar-Kyoto rat model of depression

Abstract

Background: With approximately 10% of pregnant women prescribed antidepressant drugs for the treatment of depressive disorders, there is growing concern regarding the potential long-term effects of this exposure on offspring. Research is needed in clinically relevant models to determine the effects on offspring behaviour and associated neurobiological systems. Aim: The aim of this study was to determine the effects of maternal fluoxetine treatment on anxiety-like and depressive-like behaviours in adolescent offspring as well as associated glutamatergic markers, using a clinically relevant rodent model of depression. Methods: Wistar-Kyoto (model of innate depression) and Sprague-Dawley rats were treated with fluoxetine (10 mg/kg) from gestational day 0 to postnatal day 14. Male offspring underwent behavioural testing (open field, elevated plus maze, forced swim test) at adolescence followed by quantitative immuno-detection of glutamatergic markers in the prefrontal cortex and ventral hippocampus. Results: Perinatal fluoxetine exposure exacerbated the anxiety-like and depressive-like phenotype in Wistar-Kyoto offspring and induced an anxiety-like and depressive-like phenotype in Sprague-Dawley offspring. Wistar-Kyoto offspring showed reductions in NMDA receptor NR1, NR2A and NR2B subunits, as well as post-synaptic density 95 (PSD-95) and metabotropic glutamate receptor subtype 1 (mGluR1) in the prefrontal cortex; perinatal fluoxetine exposure further reduced NR1, NR2A, PSD-95 and mGluR1 expression in Wistar-Kyoto as well as Sprague-Dawley offspring. In the ventral hippocampus perinatal fluoxetine exposure reduced PSD-95 and increased metabotropic glutamate receptor subtype 5 (mGluR5) and Homer1b/c in both Sprague-Dawley and Wistar-Kyoto strains. Conclusion: These findings suggest that maternal fluoxetine treatment exacerbates effects of underlying maternal depression on offspring behaviour, which may be mediated through alterations in the glutamatergic system. Further research investigating how to minimise these effects, whilst ensuring optimal treatment for mothers, is essential to move the field forward.

Analysis of the Gut Microbiota and Inflammatory Factors in mGluR5-Knockout Mice

“…Previous studies suggest that mGluR5 in the PFC and hippocampus may play key roles in the pathological process of depression (20). In the Western blot analysis, mGluR5 −/− mice showed normal levels of synaptic scaffold proteins (homer1 and PSD-95), ionotropic glutamate receptors (NR2A and NR2B), and extracellular regulated protein kinases (Erk1/2) in the PFC and hippocampus ( Figure 2).…”

Effect of liraglutide on neural and peripheral markers of metabolic function during antipsychotic treatment in rats

“…Western blot procedures were conducted using standard methods used in our laboratory (Jimenez Naranjo et al, 2019; Millard et al, 2019; Osborne et al, 2019a, 2019b). DVC and MBH tissue was individually homogenised (left and right hemispheres combined) in NP-40 cell lysis buffer containing 0.5 mM β-glycerophosphate, 1 mM phenylmethane sulfonyl fluoride and 1% Protease Inhibitor Cocktail, as previously described (De Santis et al, 2018).…”

GPCR signaling: role in mediating the effects of early adversity in psychiatric disorders

“…Our focus is primarily on the Gq‐coupled 5‐HT 2A R and Gi‐coupled 5‐HT 1A R pathways, and we will only briefly discuss the contributions of Gs‐coupled CRFR 1 and CRFR 2 receptors, which have been the focus of other reviews. Early stress causes alterations at multiple levels of organization spanning from molecular changes that include altered gene expression sustained via epigenetic modifications [30,37,106], cellular changes spanning from altered spine density to global dendritic architecture [46], functional and network level alterations measured predominantly via electrophysiological studies [67,73,100], and behavioral changes that are noted across a gamut of anxio‐depressive behaviors [35,107–109], fear conditioning responses [35,110–112], hallucinogen‐mediated HTR [67,113,114], sensorimotor gating [38,59,60], social approach‐avoidance behavior [35,115,116], and cognitive performance [35,65,73] (Fig. 2).…”