Neuroprotective effect of Dark Chocolate on ketamine-induced animal model of psychosis through the reversal of behavioral, biochemical and histopathological changes

The present study was designed to evaluate the antipsychotic-like activity of dark chocolate against Ketamine-induced psychosis in animals and to explore the possible underlying mechanisms for this activity. Dark chocolate (200, 400 mg/kg, along with diet), haloperidol (1mg/kg, i.p.), and olanzapine (5mg/kg, i.p) were administered daily to different groups of mice and rats; after 30 min Ketamine was injected for 21 successive days. The antipsychotic- like activity was assessed using an actophotometer, stereotypic behaviors, forced swim test (FST), and passive avoidance test. Dark Chocolate (DC) and olanzapine remarkably decreased the immobility period of Ketamine-treated mice in FST, indicating the beneficial effect of DC against depressive or negative symptoms of psychosis. There was no significant effect on the locomotor activity of the mice with the administration of DC, while it showed a reducing impact against stereotypic behaviors. Furthermore, DC significantly reduced the time taken by the rats to climb the pole, showing the effect of DC on cognition. In addition, acetylcholinesterase (AChE) activity, malondialdehyde (MDA), and tissue necrosis factor (TNF-α) levels were markedly decreased and increased GABA and enhanced reduced glutathione (GSH) levels with the treatment of DC. Furthermore, DC was also effective in reducing the ketamine induced hyperchromatic nuclei, perinuclear vacuolization, and dilated vascular channels in the cortex part of the brain. Behavioral, biochemical, and histopathological studies suggest the protective effect of DC against Ketamine induced psychosis.