CHAPTER ONE
1.0 INTRODUCTION
1.1 General Overview
Psychosis is a heterogeneous neuropsychiatric disorder characterized by distorted or non-existent sense of reality (Tandon et-al 2009). It affects about 1% of the world’s population (Picchioni et.al 2007). The prevalence of psychosis varies across the world and also within countries, with a higher rate in Nigeria compared to USA and UK (Umukoro, 2016). The proportion of adults living with psychosis per year in Nigeria was estimated to be between 0.1 and 0.4 per 1000 population (Umukoro, 2016).The major ontogenesis of psychosis are hyper-activation and dysfunction of the mesolimbic and mesocortical pathway. This generates an imbalance in the serotonergic, dopaminergic, GABAergic (gamma-aminobutyric acid-ergic) and glutamatergic neurotransmission in a certain region of the brain. Others can be traced to heredity, stress and drug abuse (Sharmaet al., 2016). Drug abuse, such as excessive intake of cannabis has been shown to increase the chances of developing psychosis by over 40% of young Nigerians (Myin-Germeys et al., 2001; Kabir et al., 2004). However, the beliefs of many Nigerians regarding the ontogeny of psychosis are divergent. They believe that psychosis is due to supernatural forces, and as such a cure cannot be found through modern medicines which in turns hinder the patronage or acceptance of modern psychotic drugs such as chlorpromazine, triflupromazine, thioridazine, trifluoperazine, fluphenazine, haloperidol, trifluperidol, penfluridol, flupenthixol, pimozide, loxapine, clozapine, risperidone, olanzapine, aripiprazole, quetiapine, ziprasidone and sulpiride (Adelekan et al., 2011).
There are different types of psychotic disorder among which is Schizophrenia.
Schizophrenia is characterized by positive (e.g., hallucinations), negative (e.g., social isolation) and cognitive (e.g., executive and memory dysfunction) symptoms (Larson et.al 2010).The positive symptoms results from hyper dopamine activity in the mesolimbic pathways, the negative and cognitive deficits emanate from hypodopaminergic system of the prefrontal cortex.(Pogarell et.al 2012)
Pharmacological treatment of Schizophrenia involves the use of antipsychotics which are divided in to first generation and second generation. The first-generation antipsychotics are responsive in reducing the positive symptoms, these agents are relatively less effective in ameliorating the negative and cognitive deficits, and are also limited by their high tendency to produce extrapyramidal side effects, due to excessive blockade of dopamine D2 receptors (Meltzer et.al 2010).In contrast, the second-generation antipsychotics are effective in ameliorating all groups of symptoms with lesser extra-pyramidal side effects, but in turn hold greater risk of cardiovascular diseases, diabetes, agranulocytosis etc.(Tandon et.al 2010). Moreover, regular intake of these agents may also increase oxidative stress and further enhance the progression of the disease(Dokuyucu et.al 2014).Pazvantogluet al. (2009)demonstrated that, the severity of the symptoms depended on the total antioxidant levels.
The brain has been reported to be more vulnerable to oxidative stress, because it is the most metabolically active tissue in the body and so generates a high load of reactive oxygen moieties, which triggers lipid peroxidation that leads to several behavioural perturbations (Dokuyucu et.al 2014).Hence, the need for newer antipsychotic agents with multipronged mechanisms of action that could target various aspects of the pathologies of schizophrenia has become imperative (Pazvantoglu et al. 2009).One source for newer drugs is medicinal plant with Indigofera arrecta as the plant of interest for this study.
Indigofera arrecta, commonly known as Bengal Indigo, Indigo, Natal Indigo, or Java Indigo, is found in tropical Africa, widely distributed throughout the continent from Senegal to Somalia, south to S. Africa. Also extending into Arabia (world agro forestry centre 2005).It is a tropical small shrub of herb growing up to 4 m in height with partly woody stems and slightly hairy leaves. It has pink or brown flowers. The leaves and roots are used externally to treat itching. The fruits and seeds are used to treat ophthalmia. The leaves are used in the treatment of diabetes, peptic ulcers, sores, gum infections, snake bites, gonorrhoea, jaundice, epilepsy, and nervous disorders (world agroforestry centre 2005). Thus the antipsychotic effect of methanol leave extract of Indigofera arrecta will be determined.
1.2 Statement of Research Problem
First-generation antipsychotics are responsive in reducing the positive symptoms of Schizophrenia, these agents are relatively less effective in ameliorating the severity of negative and cognitive deficits. They are also limited by their high tendency to produce extrapyramidal side effects, due to excessive blockade of dopaminergic D2 receptors (Meltzer et.al 2010). In contrast, the second-generation antipsychotics are effective in ameliorating all groups of symptoms with lesser extra-pyramidal side effects, but in turn hold greater risk of cardiovascular diseases, diabetes, agranulocytosis etc. (Tandon et.al 2010). It is there for important to search and find better agents that can treat both the positive, negative and cognitive symptoms of Schizophrenia and with less side effects.
1.3 Justification
Folkleric claims suggests that Indigofera arrecta may have clinical application in Schizophrenia symptomology, most especially against the negative and cognitive symptoms of the disease (pers.com, 2018). Therefore, this study is designed to scientifically validate this claim. More so herbal drugs were found to offer advantages in terms of safety and tolerability, possibly also improving patients’ compliance (Kamalipouretal., 2008).The plant is also readily available in Nigeria, thus if found to be effective and safe will be a source of cheaper, safer  and readily available treatment for Schizophrenia.
1.4 Aims
To determine the anti-schizophrenic effect of methanol leave extract of Indigofera arrecta in albino mice.
1.5 Specific Objectives
i. To determine the photochemical constituents of Indigofera arrecta
ii. To carry out acute toxicity studies of Indigofera arrecta
iii. To determine the anti-Schizophrenic effect of Indigofera arrecta using Sub chronic Ketamine Model of Schizophrenia (Ketamine induce positive symptoms, negative symptom and cognitive deficit of Schizophrenia).
1.6 Research Hypothesis
Null hypothesis: The Methanol leave extract of Indigofera arrecta lacks antipsychotic activity.
