Investigations of the Activity of Phenobarbitone in Mice Models of Depression

Abstract

Background: Depression is a severe neurological condition that interferes with the brain neurochemistry and downstream signaling pathways that are involved in the regulation of mood and behavior. Studies have highlighted the antidepressant potential of GABA mimetics such as Barbiturates and Benzodiazepines. Objective: This study investigated the activities of Phenobarbitone in acute and chronic mice models of depression. Methodology: The experimental animals received a single intraperitoneal injection of Phenobarbitone 10mg/kg, 5mg/kg, 2.5mg/kg and 0.5mg/kg respectively. Imipramine 20mg/kg was used as a positive control and 0.1mg/kg of distilled water was used as the negative control. The experimental animals were subjected to a series of stressors using neurobehavioral assays in the Forced swimming test (FST), Tail suspension test (TST), and Chronic mild stress (CMS) models of depression. The duration of immobility in the TST and FST were taken as an index of behavioral despair which is a core index of depression, while aversion to consumption of palatable solution containing 2% sucrose was also taken as index anhedonia, a symptom of depression. Result: A statistically significant decrease in the immobility time was observed in the highest dose tested i.e., 10 mg/kg Phenobarbitone (P<0.05) in both phases of the study when compared to control. There was no statistically significant decrease in the immobility time in the 5mg/kg, 2.5mg/kg, and 0.5mg/kg groups in both phases of the experiment when compared to the control. Mice subjected to the Sucrose preference test showed an increase in sucrose preference at the highest dose tested, while mice subjected to the Open field test (OFT) following exposure to CMS paradigms did not show any statistically significant increase in locomotory activity (line crossings) when compared to control. Conclusion: The result of the study indicates that Phenobarbitone possesses antidepressant activity at the highest dose tested (10mg/kg).