Sonic hedgehog pathway as a new target of atypical antipsychotics: Revisiting of amisulpride and aripiprazole effects in a rat model of schizophrenia

Schizophrenia is a chronic mental illness presented by cognitive deficits that precede its positive and negative symptoms. Sonic hedgehog (Shh)-pathway contributes to its pathophysiology. Shh has a role in neurogenesis as it regulates proliferation and survival of neural cells. In this study, effects of the anti-psychotics Amisulpride and/or Aripiprazole on the Shh-pathway and its relation to cognitive functions and neurogenesis in a rat model of schizophrenia were tested. 60 male Wistar rats were allocated into the following groups: control, socially isolated, amisulpride and/or aripiprazole-treated groups. Rats were then subjected to behavioral, biochemical, and histopathological tests to assess the impact of these drugs on Shh-pathway. Cognitive-dysfunction was evidenced in socially isolated group in novel object, three-chamber, and Morris water maze tests, associated by disorganised Shh-pathway proteins levels concentrations, increased glial fibrillary acidic protein (GFAP)-stained astrocytes. Treated groups favorably reversed these changes evidenced by increased Shh, transmembrane patched-1 and smoothened, glioma-associated-oncogene (GLI)-1 levels, dopamine-1 receptors and brain derived neurotrophic factor, and decreased GLI-3 protein, GFAP immune reaction in astrocytes and inflammatory markers compared to socially isolated group. Amisulpride and/or aripiprazole have a favorable role in turning on Shh-pathway with subsequent beneficial cognitive and neurogenesis effects.