DOPAMINE HYPOTHESIS

Lets remind ourselves how neurotransmitters work

Lets remind ourselves how neurotransmitters work

DOPAMINE HYPOTHESIS The Dopamine hypothesis states that the brain of schizophrenic patients produces more dopamine than normal brains. Evidence comes from studies with drugs post mortems pet scans

Lowering DA activity helps remove the symptoms of schizophrenia Elevated Level of Dopamine In The Brain of a Schizophrenic Patient (specifically the D2 receptor) Normal Level of Dopamine In The Human Brain Neurons that use the transmitter ‘dopamine’ fire too often and transmit too many messages or too often. Certain D2 receptors are known to play a key role in guiding attention. Lowering DA activity helps remove the symptoms of schizophrenia

ROLE OF DRUGS Amphetamines (agonists) lead to increase in DA levels Large quantities lead to delusions and hallucinations If drugs are given to schizophrenic patients their symptoms get worse

Parkinson’s disease Parkinson’s sufferers have low levels of dopamine L-dopa raises DA activity People with Parkinson's develop schizophrenic symptoms if they take too much L-dopa Chlorphromazine (given to schizophrenics) reduces the symptoms by blocking D2 receptors

POST MORTEM Falkai et al 1988 Autopsies have found that people with schizophrenia have a larger than usual number of dopamine receptors. Increase of DA in brain structures and receptor density (left amygdala and caudate nucleus putamen) Concluded that DA production is abnormal for schizophrenia

Schizophrenia or Faulty Chemicals? Chickens hatch from eggs, but a mother chicken must keep an egg warm in order for it to hatch Which Came First? The Chicken or the Egg? Schizophrenia or Faulty Chemicals? Faulty chemicals cause schizophrenia but schizophrenia may cause faulty chemicals Movie clip: house (ao2 points …… ethics & side effects of biological model approach) Drugs may influence other systems that impact on schizophrenia so cant be 100% sure about their effects

Limbic System A variety of structures under the cortex (subcortical) Many functions, including Emotion, memory formation and arousal

Limbic System Nerve pathways connect the limbic system to other subcortical structures and the cerebral cortex. Two main pathways: The Mesolimbic Pathway The Mesocortical Pathway

The Mesolimbic Pathway Connects Ventral Tegmental Area (VTA) to the nucleus accumbens. The VTA makes dopamine and sends it to the Nucleus Accumbens as a “reward” Too much dopamine or too much firing by these neurons causes Positive symptoms of schizophrenia This area is targeted by antipsychotic drugs

The Mesocortical Pathway Connects Ventral Tegmental Area (VTA) to the frontal lobe The VTA makes dopamine and sends it to the frontal lobe passing on information about emotional responses Davis et al (91) too little dopamine hits D1 receptors in frontal lobe leading to negative symptoms

Evaluation 1 Genes Genes and Family studies Concordance rates suggest genes are involved – Gottesman (1991) There may be 108 genetic loci (areas) involved – Psychiatric Genomics Consortium 2014 Ie – it’s very complicated! Surprised?

Evaluation 2 Measuring Metabolites Issue of estimating neurotransmitter levels from cerebrospinal fluid. What’s the issue? What’s the conclusion?

Evaluation 3 Role of Serotonin Conventional antipsychotics only target dopamine and work for some people Atypical antipsychotics also target serotonin receptors and work for others Suggests both are involved What does this suggest about the dopamine hypothesis?

Evaluation 4 Cause or effect Are dopamine levels caused by schizophrenia or do they cause schizophrenia?

ACTIVITY Wrote Cornell Notes on the Revised Dopamine Hypothesis Explain the role of dopamine in: The Mesolimbic Pathway The Mesocortical Pathway What is the role of each pathway in schizophrenic symptoms?

ACTIVITY Use the evaluation points to write effective AO2 commentary for the studies on the handout • You must comment on how the evidence you use supports or challenges the DA hypothesis. • You should comment on evidence both for and against the hypothesis. • You could use your own skills and knowledge to make additional critical and evaluative points.

EVALUATION POINTS There is a lack of correspondence between taking the drugs and signs of clinical effectiveness. It takes 4 weeks to see any sign that the drugs are working when they begin to block dopamine immediately. We can not seem to explain this time difference. It could be that the development of receptors in one part of the brain may inhibit the development in another. Type 1 cases respond well to conventional anti-psychotic drugs. Drugs such as CHLOPROMAZINE: Only effective at relieving the Positive Symptoms of the Illness. Not good at explaining negative symptoms. Therefore suggested that Type 2 is related to a different kind of abnormality such as brain structure. PET scans have suggested that drugs did not reduce symptoms of patients diagnosed with disorder for 10 yrs or more There may be other neurotransmitters involved. Possible that social and environmental factors trigger the condition.