Antipsychotic-like Effects of Jobelyn® in Ketamine-induced Psychosis in Mice

Abstract

Background: Jobelyn® (JB) is a polyherbal formulation with proven benefits on psychosis, a psychiatric disorder, validated in dopamine-agonist models. However, its effect in ketamine, a glutamate antagonist, is linked to schizophrenia's pathology due to N-methyl-D-aspartate (NMDA) receptor hypofunction, which remains largely unknown. Hence, this study investigates the antipsychotic effectsof JB in ketamine-induced mouse models. Methods: Antipsychotic activity of Jobelyn®(JB) (5, 10, and 50 mg/kg, p.o.) was assessed based on the inhibition of stereotyped behaviour induced by ketamine and ketamine-induced hyperactivity in mice. Ketamine-enhanced immobility in forced swim test (FST) and drug-induced ptosis and catalepsy in mice were also used to further evaluate JB's antipsychotic properties and its potential to cause extrapyramidal side effects. Results: JB (5, 10, and 50 mg/kg, p.o.) significantly (p<0.05) inhibited stereotypy induced by apomorphine (1 mg/kg, i.p.) or ketamine (10 mg/kg, i.p.) and ketamine-induced hyperactivity. Furthermore, JB significantly (p<0.05) reduced the ketamine-induced enhancementofimmobility (30 mg/kg, i.p.) in mice, suggesting antipsychotic activity. JB also dose-independently depleted the monoamine as indexed by the ptosis paradigm. However, JB (5, 10, and 50 mg/kg, p.o.) did not cause cataleptic behaviour, as it failed to alter the duration of stay of the animals on the inclined plane. Conclusion: This study provides valuable evidence that JB contains biologically active constituent with antipsychotic properties. The behavioural findings suggest possible modulation of dopaminergic and glutamatergic pathways, thus justifying its ethnomedicinal claims in the management of psychotic disorders.