Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus

Dragana Filipović, Andrijana Stanisavljević, Nebojša Jasnić, Rick E. Bernardi, Dragos Inta, Ivana Perić, Peter Gass

The dysfunction of parvalbumin-positive (PV+) interneurons, the most abundant type of hippocampal GABAergic inhibitory interneuron, has been implicated in mood disorders. We recently reported that adult male Wistar rats exposed to three weeks of social isolation show depressive- and anxiety-like behaviors and a reduced number of PV+ interneurons in all hippocampal subregions. As GABA neurotransmission has been proposed as a potential therapeutic target of antidepressant and antipsychotic medications, we examined whether treatment with the antidepressant fluoxetine (15 mg/kg/day) or the antipsychotic clozapine (20 mg/kg/day) during three weeks of social isolation in rats offered protection from the isolation stress-induced reduction in the number of PV+ interneurons in hippocampal subregions. Using immunofluorescence analysis, we revealed that both chronic fluoxetine and clozapine partially prevented the isolation-induced changes. Fluoxetine prevented the reduction in the number of PV+ interneurons in the CA2, CA3, without affecting the CA1 and dentate gyrus DG areas, whereas clozapine prevented this decrement in the CA2, CA3 and DG regions but not in CA1 areas. Moreover, fluoxetine increased the number of PV+ interneurons in CA1 in control animals. These findings suggest that chronic administration of fluoxetine or clozapine may offer partial protection from social isolation stress via modulation of the hippocampal GABAergic system.