Examinando por Autor "Doorduin, Janine"

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    A single dose of ketamine cannot prevent protracted stress-induced anhedonia and neuroinflammation in rats
    (Taylor and Francis Ltd., 2022-04) Moraga-Amaro, Rodrigo; Cyprien G. J; Reali Nazario, Luiza; Lima Giacobbo, Bruno; J. O. Dierckx, Rudi A; Stehberg, Jimmy; de Vries, Erik F. J; Doorduin, Janine
    Worldwide, millions of people suffer from treatment-resistant depression. Ketamine, a glutamatergic receptor antagonist, can have a rapid antidepressant effect even in treatment-resistant patients. A proposed mechanism for the antidepressant effect of ketamine is the reduction of neuroinflammation. To further explore this hypothesis, we investigated whether a single dose of ketamine can modulate protracted neuroinflammation in a repeated social defeat (RSD) stress rat model, which resembles features of depression. To this end, male animals exposed to RSD were injected with ketamine (20 mg/kg) or vehicle. A combination of behavioral analyses and PET scans of the inflammatory marker TSPO in the brain were performed. Rats submitted to RSD showed anhedonia-like behavior in the sucrose preference test, decreased weight gain, and increased TSPO levels in the insular and entorhinal cortices, as observed by [11C]-PK11195 PET. Whole brain TSPO levels correlated with corticosterone levels in several brain regions of RSD exposed animals, but not in controls. Ketamine injection 1 day after RSD disrupted the correlation between TSPO levels and serum corticosterone levels, but had no effect on depressive-like symptoms, weight gain or the protracted RSD-induced increase in TSPO expression in male rats. These results suggest that ketamine does not exert its effect on the hypothalamic–pituitary–adrenal axis by modulation of neuroinflammation. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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    Prenatal fluoxetine impairs non-hippocampal but not hippocampal memory in adult male rat offspring
    (NEPHB, 2021-10-01) Moraga-Amaro, Rodrigo; Díaz-Galarce, Raul; Donoso-Ramos, Juan P.; Ugalde, Valentina; Linsambarth, Sergio; Doorduin, Janine; de Vries, Erik FJ.; Ampuero, Estibaliz; Peña, Francisca; Pacheco, Rodrigo; Wyneken, Ursula; Stehberg, Jimmy
    Fluoxetine is often prescribed to treat depression during pregnancy. Rodent studies have shown that fluoxetine exposure during early development can induce persistent changes in the emotional behavior of the offspring. However, the effects of prenatal fluoxetine on memory have not been elucidated. This study evaluates the memory of adult male offspring from rat dams orally administered with a clinically relevant dose of 0.7 mg/kg fluoxetine from 9 weeks before pregnancy to 1 week before delivery. Hippocampal-dependent (Morris Water Maze, MWM) and non-hippocampal-dependent (Novel Object Recognition, NOR) memory paradigms were assessed. Anxiety- and depressive-like symptoms were also evaluated using the Open Field Test, Tail Suspension Test and Sucrose Preference Test. Male rats exposed to fluoxetine during gestation displayed NOR memory impairments during adulthood, as well as increased anxiety- and depressive-like symptoms. In the MWM, the offspring of fluoxetine-treated dams did not show learning deficits. However, a retention impairment was found on remote memory, 15 days after the end of training. Molecular analyses showed increased expression of NMDA subunit NR2B, and a decrease in NR2A-to- NR2B ratio in the temporal cortex, but not in the hippocampus, suggesting changes in NMDA receptor composition. These results suggest that in utero exposure to fluoxetine induces detrimental effects on non-hippocampal memory and in remote retention of hippocampal-dependent memory, which is believed to be stored in the temporal cortex, possibly due to changes in cortical NMDA receptor subunit stoichiometry. The present results warrant the need for studies on potential remote memory deficits in human offspring exposed to fluoxetine in utero. © 2021 Elsevier Ltd