Low-grade chronic inflammation induces behavioral stereotypy in rats

Schizophrenia is known to be associated with metabolic disturbances including diabetes mellitus, obesity and cardiovascular diseases. A growing body of evidence has suggested abnormal cytokine levels in schizophrenia. In the present study, we explored the effects of low-grade chronic inflammation on behavioral stereotypy in a rat model of non-alcoholic fatty liver disease (NAFLD). In order to induce NAFLD, rats were fed with either water enriched with 30 % fructose or plain tap water for 8 weeks. Following feeding period, behavioral stereotypy was evaluated with apomorphine-induced stereotypy test. Also, levels of tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2) and nuclear factor kappa B (NF-κB) in the liver and brain tissues were assessed biochemically. Brain homovanilic acid (HVA) was measured to evaluate the dopamine turnover. NAFLD rats showed significantly higher stereotypy score compared to controls (p = 0.016). TNF-α, IL-2, and NF-κB levels were significantly increased in NAFLD rats compared to control group. Brain HVA levels were elevated in NAFLD rats as well (p = 0.008). Moreover, NAFLD group prompted a considerable increase in brain IL-2 immunoexpression (p = 0.005). In conclusion, the present study demonstrates that low-grade chronic inflammation such as NAFLD may enhance apomorphine-induced stereotypic behavior via increasing dopaminergic activity in rats.