Effect of aripiprazole and improved living conditions on behavioral manifestations and neurogenic markers expression in an animal model of PTSD.

Objective. Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder that can develop after exposure to a severe traumatic event and is connected with behavioral changes and adult neurogenesis impairment. Atypical antipsychotics including aripiprazole (ARI) or enriched environment can ameliorate disturbances connected to PTSD. This study was aimed to reveal whether ARI treatment supplemented by improved living conditions, i.e. toy rotation (TR), will ameliorate behavioral outcomes and reverse assumed changes in neurogenesis more effectively than sole ARI treatment in a single prolonged stress (SPS) animal model of PTSD. Methods. Adult male Sprague-Dawley rats weighing 176-200 g were randomly assigned to 5 experimental groups: (1) VEH - control non-stressed animals injected with vehicle (VEH, 2% Tween 20 in the saline); (2) SPS - animals exposed to SPS injected with VEH; (3) SPS+ARI - SPS animals injected with ARI (5 mg/kg in VEH); (4) SPS+TR - SPS animals exposed to TR and injected with VEH; (5) SPS+ARI+TR - SPS animals exposed to TR and injected with ARI. Animals in TR groups were housed in the standard cages with two toys per cage, which were replaced every other day. Elevated plus maze (EPM), open field (OF), and novel object recognition test (NOR) were used to assess the anxiety-like behavior and learning/memory. Changes in gene and protein expression of selected neurogenic markers (BDNF, GFAP, Sox2, DCX, NeuN) and transcription factors (ΔFosB, pCREB) in the subventricular zone (SVZ) and the gyrus dentatus (GD) of the hippocampus were determined by semi-quantitative real-time PCR and immunohistochemistry, respectively. Results. SPS animals showed increased anxiety-like behavior that was suppressed by TR and ARI+TR treatment combination. Although SPS did not affect the expression of studied neurogenic markers, ARI treatment increased the expression of doublecortin in the SVZ and TR increased expression of NeuN in the GD of PTSD-like animals. TR enhanced ARI effect on NeuN expression in the SVZ. SPS induced increase of ΔFosB positive cells, which was reduced by ARI+TR complementary treatment. Conclusions. Obtained results indicate that TR, in contrary to ARI, suppressed the anxiety-like behavior in PTSD-like animals. SPS does not affect the neurogenic markers expression in the SVZ or GD, but ARI and TR or their combination seems to increase the survival of the newborn cells.