EVALUATION OF ANTPSYCHOTIC EFFECTS OF METHYL JASMONATE IN MICE

Abstract

Psychosis is a chronic neurological disorder that impairs the quality of life of the patients and remains a major health challenge worldwide. Current drugs used to manage psychosis are expensive and only provide symptomatic relief without altering the underlying pathological derangement. Methyl jasmonate (MJ) is a bioactive compound known to have beneficial effects against a wide range of neurological disorders. However, its usefulness in treatment of psychosis has not been scientifically proven. Thus, this study was undertaken to investigate the effects of MJ on psychosis in animal models. Fifty male Swiss mice (23.5±1.5 g) were assigned to 10 groups to evaluate acute antipsychotic-like effect of MJ on bromocriptine or ketamine-induced stereotypy. Groups 1-5 received 1% ethanol (vehicle, 10 mL/kg, i.p.), MJ (25, 50, 100 mg/kg, i.p.) and haloperidol (1 mg/kg, p.o.) 60 minutes prior to bromocriptine (5 mg/kg, p.o.) treatment, while groups 6-10 received vehicle (10 mL/kg, i.p.), MJ (25,50,100 mg/kg, i.p.) and risperidone (0.5 mg/kg, p.o.) 60 minutes prior to ketamine injection. Thereafter, each mouse was placed independently in an observation chamber (20 cm × 20 cm × 23 cm) and stereotyped behaviours were observed for 2 min at 10, 15, 30, 45 and 60 min after bromocriptine or ketamine injection. Another 36 mice (n = 6) were also allotted into treatment groups. Group 1 received vehicle (10 mL/kg, i.p.) while groups 2-6 were treated with ketamine (20 mg/kg, i.p.) once daily, for 14 days. Then, from 8th to 14th day, group 2 was treated with vehicle (10 mL/kg, i.p.) while Group 3-6 received MJ (25,50.100 mg/kg, i.p.) and risperidone (0.5 mg/kg) 60 minutes after ketamine injection. Hyper-locomotion was then measured as an index of psychotic-like behaviour using the open field chamber while memory was assessed using the Y-maze. Thereafter, whole brain samples were used to assay for malondialdehyde, reduced glutathione (GSH), catalase and Superoxide Dismutase (SOD) using spectrophotometric techniques. Histology of prefrontal cortex, hippocampus and substantial nigra were viewed in ketamine-treated mice and neuronal density was determined. Data were analysed using descriptive statistics and ANOVA at α0.05. Methyl jasmonate (25, 50 and 100 mg/kg) significantly reduced stereotypy score (0.62±0.21, 0.24±0.10 and 0.06±0.04) relative to vehicle (1.84±0.15) and (0.50±0.08, 0.36±0.06, 0.26±0.07) relative to vehicle (1.52±0.10) induced by bromocriptine and ketamine, respectively. Methyl jasmonate significantly ameliorated ketamine-induced hyper-locomotion (74.67±4.70, 75.67±2.88, 78.00±4.16 s) compared to vehicle (185.0±3.63) and memory deficit (80.1±2.8, 71.2±2.9, 57.0±3.4 %) relative to vehicle (53.7±2.0%). Methyl jasmonate reduced malondialdehyde concentration (19.96±1.64, 22.84±1.16, 24.65±1.70 μmol/g tissue) relative to vehicle (33.72±2.28 μmol/g tissue) but increased GSH levels (47.43±2.22, 42.23±2.83, 37.26±1.84 μmol/g tissue) compared to vehicle (21.95± 2.69 μmol/g tissue). Methyl jasmonate also increased catalase level in the brain homogenate (86.63±4.65, 83.36±4.24, 76.06±3.22 units/mg protein) relative to vehicle (59.91±3.94 units/mg) and SOD (27.52±1.63, 24.41±1.49, 19.71±1.59 units/mg protein) compared with vehicle (13.08±1.33 units/mg protein), respectively. Brain histology revealed that MJ has protective property on neuronal cells compared to ketamine-treated mice. Methyl jasmonate demonstrated antipsychotic property via activation of antioxidation pathway in Swiss mice.