OBJECTIVE: To probe into whether olanzapine plays the role of neuroprotection on schizophrenic model rats through phosphatidylinositol-3-kinase（PI3 K）/protein kinase B（Akt） pathway. METHODS: Schizophrenic model rats were established and divided into model group

LY294002（PI3 K/Akt pathway inhibitor） group

olanzapine group and olanzapine+LY294002 group

with 12 rats in each group; another 12 SD rates were set as control group. After grouping

the rats’ stereotyped behavior and ataxia were scored; hematoxylin-eosin staining was used to detect the pathological changes of hippocampal neurons of the rat brain; the water maze test was used to detect the cognitive function; enzyme linked immunosorbent assay was used to detect the serum interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） levels; Western blotting was used to detect the expression of PI3 K/Akt pathway-related proteins in brain tissue. RESULTS: Compared with the control group

the hippocampus of model group showed a reduction in the number of neuronal cells

sparse alignment

shrinkage of the nucleus

unclear cytoplasm and nucleolus structure

deep staining

pathological damage like cell apoptosis and necrosis; scores of stereotyped behavior and ataxia

serum IL-6 and TNF-α levels were significantly increased

the average escape latency of water maze test was significantly prolonged

the frequency of crossing original platform was significantly reduced

the brain tissue pPI3 K/PI3 K and p-Akt/Akt were significantly decreased

with statistically significant differences（P< 0. 05）.Compared with the model group

the pathological damage of hippocampal neurons of olanzapine group was relieved

scores of stereotyped behavior and ataxia

serum IL-6 and TNF-α levels were significantly reduced

the average escape latency of water maze test was significantly shortened

the frequency of crossing original platform was significantly increased

brain tissue p-PI3 K/PI3 K and p-Akt/Akt were significantly increased

with statistically significant differences（P<0. 05）. Compared with the model group

the pathological damage of hippocampal neurons of LY294002 group was aggravated

scores of stereotyped behavior and ataxia

serum IL-6 and TNF-α levels were significantly increased

the average escape latency of water maze test was significantly prolonged

the frequency of crossing original platform was significantly reduced

the brain tissue p-PI3 K/PI3 K and p-Akt/Akt were significantly decreased

with statistically significant differences（P< 0. 05）. Compared with the LY294002 group

the pathological damage of hippocampal neurons of olanzapine +LY294002 group was relieved

scores of stereotyped behavior and ataxia

serum IL-6 and TNF-α levels were significantly reduced

the average escape latency of water maze test was significantly prolonged

the frequency of crossing original platform was significantly increased

brain tissue p-PI3 K/PI3 K and pAkt/Akt were significantly increased

with statistically significant differences（P< 0. 05）. Compared with the olanzapine group

the pathological damage of hippocampal neurons of olanzapine + LY294002 group was aggravated

scores of stereotyped behavior and ataxia

serum IL-6 and TNF-α levels were significantly increased

the average escape latency of water maze test was significantly prolonged

the frequency of crossing original platform was significantly reduced

the brain tissue p-PI3 K/PI3 K and p-Akt/Akt were significantly decreased

with statistically significant differences（P<0. 05）. CONCLUSIONS: Olanzapine can play the role of neuroprotection on schizophrenic model rats by activating PI3 K/Akt pathway.