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Objectives: Although the relation between psychotic behavior and immune abnormalities has taken attention for many years, it remains to be elucidated whether the alterations in cytokine levels are part of etiology or result of the stress associated with the disorder. In the light of the previous studies about cytokine level alterations due to metabolic changes and psychosis, we hypothesized that fatty liver might potentiate apomorphine-induced stereotypy in a rodent model and that a synthetic GLP-1 analog, exenatide would ameliorate this effect.
Methods:18 male Sprague Dawley albino mature rats were used; 30% fructose was given in drinking water for 8 weeks in order to induce the hepatosteatosis. The animals were divided into three groups (normal group, intra cerebro ventricular (ICV) exenatide group and ICV NaCl group). Apomorphine-induced stereotypic behavior test was performed in all groups and the liver was removed for histopathological examination after all the rats were euthanized. Apomorphine-induced stereotypic behavior test Signs of stereotypy, which include mainly sniffing and gnawing, were served and scored as follows: absence of stereotypy (0), occasional sniffing (1), occasional sniffing with occasional gnawing (2), frequent gnawing (3), intense continuous gnawing (4), intense gnawing and staying on the same spot (5). The stereotypic behavior was rated after each minute and mean of 15 min period was calculated and recorded.
Results: In nonalcoholic fatty liver (NAFL) group, stereotypy scores were significantly increased compared to the control group rats (p < 0.00001). Significant decreases in stereotypy scores were observed in ICV exenatide group with NAFL when compared to ICV saline group with NAFL (p<0.005). Also, brain MDA and TNFα levels decreased in exenatide treatment group.
Conclusions: In the present study, we demonstrated that fatty liver enhanced the effects of apomorphines on stereotypy, which was reversed by exenatide possibly via antioxidant and anti-inşammatory effects.