Olanzapine effects on parvalbumin/GAD67 protein expression in the layers of the retrosplenial cortex in chronically socially isolated rats

Abstract

The alterations of gamma-aminobutyric acid (GABA) neurotransmission induced by psychosocial stress are implicated in the pathophysiology of major depressive disorder and anxiety. Olanzapine (Olz), an atypical antipsychotic, is used to treat psychiatric disorders. Since GABAergic signaling has been proposed as a potential therapeutic target for antipsychotics, we aimed to determine the susceptibility of different layers (1;2/3/4;5/6) in the retrosplenial cortex (RSC), including both granular c (RSGc) and dysgranular (RSD) subregions, in adult male rats exposed to chronic social isolation (CSIS) (six weeks), an animal model of depression, and/or treatment with Olz (7.5 mg/kg/day) (lasting 3 weeks of six-week CSIS), on the protein expression of parvalbumin interneurons, the largest class of GABAergic inhibitory neurons, and glutamate decarboxylase 67 (GAD67), as the main GABA-synthesizing enzyme. Results showed that CSIS decreased the number of GAD67 positive (GAD67+) cells in 5/6 layers of RSGc and increased in 1 and 2/3/4 layers of RSD, with no significant effect on PV positive (PV+) cells. Treatment with Olz in CSIS rats increased the number of GAD67+ cells in the 5/6 layers of the RSC and decreased in 1 and 2/3/4 layers of the RSD. Regarding PV+ cells, Olz treatment led to a decrease in 2/3/4 layers of RSD with no significant effect in RSGc. Overall, this study provided an insight into the neuroinhibitory transmission in the RSC, at the level of subregions and layers following CSIS and/or Olz treatment, and its involvement in the rat model of depression.