INVESTIGATIONS OF ACTIVITY OF PHENOBARBITONE IN MICE MODELS OF DEPRESSION

INVESTIGATIONS OF ACTIVITY OF PHENOBARBITONE IN MICE MODELS OF DEPRESSION

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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.

CHAPTER ONE

1.0 Introduction

Depression is a severe neurological condition that interferes with the brain neurochemistry and synaptic processes, ultimately leading to intense expression of our emotions. This is evident from studies on neural tissues and grey matter of most patients suffering from depression and other forms of neurological anomalies (Xiao-Li et al., 2015). Severe forms of depression also lead to the atrophy of vital brain regions that are involved in the regulation of mood and behaviour such as the limbic system, prefrontal cortices and the hippocampus (Li et al., 2015).

Depression is characterized by a myriad of clinical symptoms including generalized decrease in mood, behavioural despair, melancholia, loss of interest in previously enjoyed activities (anhedonia) and a decrease in cognitive and motor skills which becomes persistent for at least two or more weeks. Severe depression leads to constant suicidal ideation or possible suicide, according to the diagnostic and statistical manual of mental health DSM-V criteria as edited by the American Psychiatric Association (APA) (Mayes and Horwitz, 2005).

Depressive episodes have been broadly classified into unipolar and bipolar depression. There is a very little difference between the two types of depression and often times they occur together (Daniel and Nick, 2011). Unipolar depression is mostly seen in normal physiological without an underlying pathological condition or mania, such as during pregnancies, in adolescents, ultradian rhythms or due to chronic stress and other metabolic diseases such as diabetes and hypertension (Jonathan and Mark 2012).

Bipolar depression on the other hand presents clinical symptoms of depression with mania and psychoses. Studies have shown that it is mostly comorbid with most psychiatric illnesses and is often accompanied by manic episodes, distorted thoughts and hallucinations (Driessen, et al., 2010).

In 2011, the World Health Organization (WHO) ranked depression as the fourth leading cause of morbidity and by the year 2020, it is projected to be the main cause of disease burden worldwide (Jean and Mike, 2011). Depression leads to a significant decrease in the quality of life of most patients and hinders interpersonal relationships, and work output per person, thus leading to significant impairment in day to day activities (Anita et al., 2012).

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Globally, over 120 Million people are affected with depression and s


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