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.