Melatonin modulates inflammatory mediators and improves olanzapine-induced hepatic steatosis in rat model of schizophrenia.

BACKGROUND

Melatonin (Mel) has lower levels and can be used as monotherapy in schizophrenia. Mel alleviated liver steatosis induced by atypical antipsychotics.

GOALS

To investigate Mel effect as monotherapy and addon treatment on ketamine-induced behavioral changes in rat schizophrenia model and olanzapine (Ola)-induced metabolic derangement.

METHODS

24 male rats divided into four groups; C: control; O: Ola; OM: Ola plus Mel and M: Mel. All groups treated orally daily for 25 days. We measured activities of daily life (ADL) and rat performance in radial arm water maze (RAWM) before and after ketamine (Ket) injection, serum level of liver enzymes, lipoproteins, sugar, inflammatory markers and liver histopathology.

RESULTS

Ket significantly reduced burrowing and hoarding behavior, increased working memory errors (WME) and time to reach target (TRT). Ola antagonized the deleterious effects of Ket on ADL, WME and TRT. Mel monotherapy significantly reduced burrowing and doesn't affect hoarding, WME or TRT in RAWM. Significant rise in ALT, AST, IL-1 beta, IL-6, IL-10, TNF-alpha, LDL, TGs and hepatic steatosis score (HSS) in O compared to C group. Co administration of Mel significantly decreased ALT, AST, IL-1 beta, IL-6 and TNF alpha. Insignificant difference in IL-10, TGs or LDL and significant improvement in HSS in OM compared to O group. Insignificant change in HDL or blood sugar in both O and OM groups compared to C group detected.

CONCLUSION

Although ineffective as monotherapy, Mel co administration provides promising natural way to improve Ola-induced hepatic derangement in psychotic disorders.