Probable mechanisms involved in the antipsychotic-like activity of methyl jasmonate in mice

Abstract

Psychosis is a chronic neuropsychiatric disorder that affects millions of individuals worldwide and impairs the quality of life and productivity of the patients. The clinical efficacy of antipsychotic drugs has been compromised by adverse effects, relapse, and therapeutic failures, thus necessitating search for alternative agents. Methyl jasmonate (MJ) is a bioactive compound reported to have beneficial effects in various neurological disorders. This study was undertaken to investigate the antipsychotic-like effects of MJ in mice. Male Swiss mice were pretreated intraperitoneally with MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min prior to bromocriptine (5 mg/kg) or acute injection of ketamine (10 mg/kg). Thereafter, each mouse was observed for stereotype behaviors for 2 min at 10, 15, 20, 30, and 45 min post-bromocriptine injection. Another set of mice received MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min after chronic ketamine injection (20 mg/kg, i.p) once daily for 14 consecutive days. Afterwards, locomotor activity and memory function in this sequence were evaluated using open field and Y-maze tests. The levels of malondialdehyde (MDA) and glutathione (GSH) and activity of catalase and superoxide dismutase (SOD) in the brain were determined. MJ significantly inhibited stereotypy behavior induced by bromocriptine or acute ketamine injection, which suggest antipsychotic-like activity. It also attenuated hyper-locomotion and memory deficits induced by chronic injection of ketamine in mice. The increased oxidative stress as shown by the altered brain levels of MDA, GSH, and activity of antioxidant enzymes induced by chronic injection of ketamine was reduced by MJ. Taken together, these findings suggest that MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission.

Morin Pretreatment Attenuates Schizophrenia-Like Behaviors in Experimental Animal Models

“…Thirty minutes thereafter, each animal from groups 2-7 received intraperitoneal injection of apomorphine (APO) (2 mg/kg) and mice were placed immediately in a transparent observation chamber (20 cm × 20 cm × 23 cm), and ste-reotype behaviors were observed for 2 min at 5, 10, 20, 30, 40, 50 and 60 min after APO injection according to the stereotype behavioral scale: 0 = absence of stereotype behavior; 1 = presence of stereotype movements of the head; 2 = intermittent sniffing; 3 = chewing; 4 = intense licking. Thereafter, Kruskal-Wallis test was used for the statistical analysis, which was performed separately to the time points at 5, 10, 20, 30, 40, 50 and 60 min, as previously described [30]. After each mouse session, the observation chamber was cleaned with 70 % ethanol to remove residual odour from previous mouse.…”

Methyl Jasmonate: Behavioral and Molecular Implications in Neurological Disorders

“…[ 16 ], which have shown that MJ exhibited sedative effect and enhanced GABAergic neurotransmission. These findings have led to extensive studies on the effects of MJ on neurological disorders and the mechanisms underlying its neuroprotective activity in rodents [ 17 - 23 ]. This review presents the documented evidence on the neuroprotective activities of MJ and the mechanisms underlying its therapeutic potentials in neurological disorders.…”

Methyl Jasmonate Ameliorates Unpredictable Chronic Mild Stress‐Induced Behavioral and Biochemical Alterations in Mouse Brain

“…Although MJ is widely used to treat depression, nervousness, and improve memory in aromatherapy, the finding that MJ demonstrated sedative effect and enhanced GABA currents [Hossain et al, ] provided the first experimental evidences supporting a mechanistic basis for its therapeutic benefits in neuropsychiatric disorders. Moreover, MJ demonstrated adaptogenic, antiamnesic, and antipsychotic activities in rodents [Eduviere et al, ; Umukoro et al, ; Annafi et al, ] and exhibited antidepressant‐like activity in mice subjected to acute stress models of forced swimming (FST) and tail suspension (TST) tests. It also attenuated depressive‐like symptoms induced by lipopolysaccharide in mice [Umukoro et al, ; Adebesin et al, ].…”