Download dopamine hypothesis

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
Normal Level of
Dopamine In The
Human Brain
Elevated Level of Dopamine
In The Brain of a
Schizophrenic Patient
(specifically the D2 receptor)
 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
hatch from
eggs, but a
mother
The Chicken or the Egg?
chicken
must keep
an egg warm
in order for
it to hatch
Schizophrenia or Faulty
Chemicals?
Which Came First?
Faulty chemicals cause
schizophrenia but schizophrenia
may cause faulty chemicals
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.