DOPAMINE HYPOTHESIS AO1

• L-dopa to treat Parkinson’s disease


  1950s, research was looking at the role of dopamine in Parkinson’s disease, which is a neurological condition which causes tremors and slow, imprecise movements. It was discovered that the drug L-Dopa, increases the level of dopamine in the brain, which reduces the symptoms of Parkinson’s. However, the aftereffects of the individuals who had taken the drug, showed similar behaviour to those who have schizophrenia.
• Excessive dopamine link to schizophrenia


  L-dopa symptoms proved there to be a link between dopamine and schizophrenia. It was understood that schizophrenia was caused by excessive amounts of dopamine. This was caused by neurons firing dopamine too often or too quickly, this ‘overload’ is likely to lead to the symptoms of schizophrenia.
• conclusions on dopamine hypothesis 


  Delay, Deniker & Harl discovered antipsychotic drugs in 1952. Then Carlsson & Lindqvist realised that these drugs caused an increase in the metabolism of dopamine. Lastly, numerous studies had shown that amphetamine can induce psychotic symptoms and reserpine could treat them. However, the hypothesis couldn’t be as simple as that as the drugs introduced were only to reduce the levels of dopamine which literally had little or no effect on individuals who suffered from the negative symptoms of schizophrenia mainly.
• Dopamine Receptor Sites


  There are 5 receptor sites: D1-D5. They are widely distributed in the cerebral cortex and the limbic system.
• role of D2 receptor on schizophrenia

  The D2 receptor was particularly of interest during Seeman and Lee’s research in 1975, as antipsychotic drugs were seen to mainly target this specific receptor. This led to the main focus of research towards the limbic system.
• role of the left amygdala on schizophrenia 


  Owen et al investigated, in 1987, through autopsies that generally there is an increase in the amount of dopamine in the left amygdala. The left amygdala’s role is linked to emotions and memory.
• role of the striatial area on schizophrenia

  Falkai et al in 1988 found out that there was increased dopamine in the striatal areas such as the caudate nucleus and the putamen (they play an important role in the brain's learning and memory system).
• role of D1 receptors in schizophrenia

  Davis et al (1991) suggested that the effects of abnormal dopamine activity could vary by brain region. In the frontal lobe, it could be seen that the levels of dopamine activity were low. This could account for the negative symptoms of schizophrenia. Therefore this showed the imbalance of dopamine, as too little was going to the frontal lobe but too much was going to the striatal areas; and the fact that D1 receptors link to negative symptoms and D2 receptors linked to positive symptoms.
• Two pathways of the limbic system that play in schizophrenia

  Two of the main pathways linked to schizophrenia are the mesolimbic pathway and the mesocortical pathway.
• The mesolimbic pathway 


  The mesolimbic pathway carries signals from the ventral tegmental area to the nucleus accumbens. Too much dopamine, either from neurons that fire too often or too quickly, cause overstimulation and the positive symptoms of schizophrenia such as hallucinations or delusions.

  Antipsychotic drugs reduce dopamine activity in this pathway and lead to the reduction of the positive symptoms of many people with schizophrenia.
• The mesocortical pathway


  The mesocortical pathway carries signals from the ventral tegmental area to the frontal lobe. The pathway is important in emotional responses, motivation and cognition. Kenneth Davis et al (1991) suggested that too little dopamine (‘hypofunction’) is evident in D1 receptors of the frontal lobe of many individuals with the cognitive impairments and negative symptoms of schizophrenia.
• Current research on dopamine‘s role in schizophrenia


  The advancement in the last 20 years in imaging has allowed researchers to track neurotransmitter function. These studies confirm that the striatal dopamine is much higher in patients with schizophrenia and it is closely linked to the psychotic symptoms. Imaging has also shown that blocking the excess activity either by blocking dopamine release or by blocking the postsynaptic receptors leads to reduced symptoms.