Chronic social isolation reduces parvalbumin-positive interneurons in the medial prefrontal cortex of adult rats: protection by fluoxetine and clozapine

author: Nevena Todorović, Vinča Institute of Nuclear Science, University of Belgrade
published: Oct. 1, 2015,   recorded: May 2015,   views: 1519


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Depression is one of the leading causes of disability worldwide. Recent studies have indicated that there is a link between depressive symptoms and disregulation of GABAergic system. Decrement of parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC), brain area highly implicated in depressive symptomatology, has been observed in psychiatric patients. We aimed to determine whether chronic social isolation of adult male Wistar rats for a period of 21day, which represents an animal model of depression, affects the number of PV-positive interneurons in medial precentral (PrCm) area, cingulate cortex, area 1 (Cg1), prelimbic (PrL), infralimbic (IL) area and dorsal peduncular cortex (DP) of mPFC. Since GABAergic signaling has been proposed as a potential therapeutic target for antidepressants or antipsychotics, we examined if the treatment with antidepressant fluoxetine, a selective serotonin reuptake inhibitor (15mg/kg/day) or atypical antipsychotic clozapine (20mg/kg/day) administered during the 21day may offer the protection from eventual isolation-induced alternation in PV-positive GABAergic interneurons. Results of immunofluorescence analysis revealed that social isolation reduced number of PV-positive interneurons in all examined areas of mPFC. Fluoxetine prevented reduction of number of these GABAergic interneurons in PrCm, PrL and DP, while clozapine only protected PrCm and PrL area. Finally, fluoxetine administration to control rats caused decrement in number of PV-positive interneurons in Cg1, while clozapine-treated control animals exhibited reduced number of these interneurons in DP. In summary, chronic administration of fluoxetine and clozapine showed area specific protection of PV-positive interneurons in the mPFC from deleterious effect of chronic social isolation.

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