Interaction of Toxoplasma gondii and ketamine-induced psychosis: Behavioral, histopathological and neurochemical effects in a murine model.

Background: According to studies, this parasite can change how the infected mice behave and potentially influence human behavioral attributes. T. gondii and psychosis have been linked in several studies. Psychosis is a severe neuropsychiatric illness with uncertain etiology. The mechanism that causes the host's behavior to change is unknown and more studies are needed. Objective: To investigate the effect of T. gondii infection and ketamine-induced psychosis on certain behavioral alterations, as well as alterations at the cellular and neurotransmitter levels. Material and Methods: Sixty mice were employed in this study that assigned into five groups. Group I is the uninfected control. Group II is an infected group with the ME49 strain of T. gondii. Group III is the ketamine induced-psychosis group. Group IV is the combined one where the mice were infected by T. gondii ME49 strain then received ketamine. Group V is a combined treated group with spiramycin. Behavioral tests, histopathological changes, immunohistochemical for brain astrocytes, neurochemical analysis for acetylcholinesterase (AchE) and molecular study for tyrosine hydroxylase (TH) gene expression were investigated. Results: Mice of Toxoplasma-infected (GII) and induced-psychosis (GIII) and the combination of both (IV) showed increased locomotor activity, anhedonic-like symptoms and impaired memory. A significant decrease in the pyramidal cell layer thickness and the hippocampal total area also was reported. Gliosis was the feature detected immunohistochemically. AchE activity and TH gene expression were increased in all groups compared to the uninfected control. The most prominent changes were in the combined group (GIV). Conclusion: The interplay between T. gondii and induced psychosis was explored, highlighting how both conditions are associated with behavioral, histopathological and immunohistochemical changes and alternation in the activity of two important neurotransmitters. The interaction is multifactorial and necessitates further research to elucidate the underlying biological pathways and establish causality.