INVESTIGATIONS OF ACTIVITY OF PHENOBARBITONE IN MICE MODELS OF DEPRESSION

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Department of Medicine

ABSTRACT
Depression is a severe neurological condition that interferes with our brain neurochemistry and synaptic processes, ultimately leading to intense expression of our emotions. Major fallouts observed from the use of antidepressant including high rates of remission, impotency and suicidal tendencies led to researches to screen other compounds with antidepressant potentials. Various studies have highlighted the antidepressant potential of GABA mimetics such as Barbiturates and Benzodiazepines. This study investigated the antidepressant potential of Phenobarbitone in mice models of depression. A total of 108 Adult male Swiss Albino mice were used throughout the study. The study was conducted in two phases: an acute and a chronic phase respectively. Each mouse received a single intraperitoneal injection of Phenobarbitone 0.5 mg/kg, 2.5 mg/kg, 5 mg/kg and 10 mg/kg respectively. Imipramine 20mg/kg served as the standard drug while distilled water (10 ml/kg) was used as the vehicle. The mice were subjected to a series of stressors using the Forced swimming test (FST), Tail suspension test (TST) and Chronic mild stress (CMS) models of depression, and the duration of immobility in the TST and FST were taken as a sign of behavioral despair, while decrease in sucrose preference was taken as sign of anhedonia, which are core symptoms of depression. The acute phase of the study lasted for just a day while the chronic phase lasted for 30 days. A statistical significant decrease in mean immobility time was observed at the highest dose tested i.e. 10 mg/kg treatment group (p<0.05) when compared to control in both phases of the study i.e. Acute phase: TST126.1 ± 11.34*, FST54.5 ± 7.34*, Chronic Phase: FST54.5 ± 7.34* and SPT 24.5 ± 1.06*. The mice were further subjected to the open field (OFT) which showed no significant increase in locomotory activity (line crossings) in all the treatment groups when compared to control, this indicates that the results obtained from both phases of the study was due to antidepressant potential of Phenobarbitone and not due to increase in locomotory or due to the stimulant effect of the Phenobarbitone. This study shows that phenobarbitone possess significant antidepressant potential at 10 mg/kg group (p<0.05) when compared to control in both phases of the study.