Dopamine Hypothesis Of Schizophrenia

Schizophrenia has been defined as a mental disorder characterized by a breakdown in mental thinking and a poor emotional response. This disorganization hasn’t till now acquired a clear understanding of the mechanisms that lie behind (Harrison 1999) but researchers suggest an increase in the dopaminergic transmission in the prefrontal cortex coupled to an inhibition of the glutamatergic pathways, majorly at the level of NMDA receptors (Wen-Jun Gao). For more than 50 years, the dopamine hypothesis had been considered the mother of the theories of schizophrenia. Van Rossum first proposed it in 1966 suggesting that a hyperactivity occurring at the level of the mesolimbic dopamine pathway is the mediator of positive symptoms of schizophrenia (Seeman 1987). More research has flaunted a hypoactivity in the mesocortical dopamine pathway, which has been hypothesized to mediate the negative, cognitive, and affective symptoms of schizophrenia (Knable & Weinberg 1997; Tzschentke 2001). However, in the past two decades, hypotheses of schizophrenia focused less on the already established facts of the hyperactivity of mesolimbic dopamine neurons and under-activity of the mesocortical dopamine neurons. A major hypothesis of schizophrenia digging, to a certain extent, far from dopamine proposes that a combination of genetic factors converge on the N-methyl-D-aspartate (NMDA) receptor of the excitatory neurotransmitter glutamate, leading to neurodevelopmental abnormalities in glutamate synapse formation and ultimately resulting in the observed hypofunction at the level of NMDA receptors. Knowing that NMDA receptors regulate dopaminergic neurons, the decreased activity of NMDA receptors may be involved in the abnormal dopamine activity associated ...

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...ng pubertal period and leads to the loss of around 40% of the synaptic connections in order to improve working memory and higher linguistic ability is taken too far leaving fewer synapses in the frontal and temporal lobes (Feinberg 1983). This is usually associated with abnormality in Glutamate and Dopamine transmission. It was previously reported that substance abuse early in adolescence such as the abuse of an antidepressant can induce schizophrenia in people and many drugs were already tested on animal models such as the Amphetamine and Phencyclidine PCP (Mouri et al. 2007), hence the idea of using Bromocriptine, a psychotic drug to induce schizophrenia in mouse models and by that proving that this drug can induce schizophrenia in people especially when it is administered early during puberty where abnormal neural changes might occur due to overuse of such drugs.