Carlsson Study Flashcards
What is the aim of Carlsson’s study?
One aim is to present the current view of the relationship between SZ and dopaminerfic dysfunction
Another aim is to explore other theories like glutamaterfic deficiency or hypoglutamatergia
What did Carlsson discover when he revisited the dopamine hypothesis?
There is continuing evidence to support this hypothesis, for example PET studies show that the drug amphetamine enhances schizophrenia like symptoms in people with schizophrenia more than controls. However, this explanation is insuffiecent as it does not apply to all people with SZ
What did Carlsson discover when he talked about beyond dopamine?
It is unlikely that dopamine is the only neurotransmitter in the brain associated with SZ. Interest has focused on glutamate because it was found that PCP induces SZ like symptoms and is a powerful antagonist of NDMA receptors - a type of glutamate receoptor. The effect is that glutamate is decreased and this increases dopamine activity, acting like an accelerator.
What did Carlsson discover when he talked about Glutamatergic control of dopamine release?
Glutamate seems to regulate the behaviour of dopamine and sheds some light on the behaviour of dopamine in the brain. Carlsson describes how it acts as an “accelerator” (increasing dopamine activity) or a “brake” (decreasing it).
What did Carlsson discover when he talked about the Glutamate-dopamine interaction at the postsynaptic (striatal) level?
Low levels of glutamate (hypoglutamatergia) seems to link with both positive and negative schizophrenic symptoms. Carlsson locates this activity in an area of the brain called the striatum (in the basal ganglia) and in the cerebral cortex (which includes the frontal lobe, where conscious behaviour happens).
What did Carlsson discover when he talked about The thalamic filter?
Carlsson has his own theory about what’s going on. The thalamus is an important brain structure between the stratium and the cerebral cortex. Carlsson proposes that the thalamus “filters off” neurortransmitters coming out of the stratium to stop the cerebral cortex from overloading. There are two “pathways” through the thalamus: the indirect pathway or the direct pathway
What did Carlsson discover when he talked about Comparing two experimental schizophrenia models - therapeutic implications?
This leaves us with two models (explanations) for schizophrenia: hyperdopaminergia (too much dopamine) or hypoglutamatergia (too little glutamate).
Some patients respond better to some drugs than others and this might be because some people's schizophrenia is more dopaminergic and other people's symptoms are more glutamatergic The "treatment resistant" patients who don't respond to typical antipsychotics (that reduce dopamine) might have a more glutamatergic condition instead Clozapine is an atypical antipsychotic that has better results with "treatment resistant" patients and this might be because it doesn't target dopamine (it targets serotonin instead)
What did Carlsson discover when he questioned is the therapeutic potential of dopaminergic agents exhausted?
Should we give up on dopaminergic antipsychotics and start focusing on glutamates instead? Carlsson thinks there’s still a future in dopamine research.
Carlsson et al. are researching new drugs which regulate dopamine activity without producing harmful hypodopaminergia (which creates the unpleasant side-effects of antipsychotics) These work by acting at the pre-synapse (where dopamine is produced) rather than the post-synapse (where the dopamine receptors are), so they stop the brain producing too much dopamine without interfering with the brain's ability to process dopamine normally These drugs are "now in clinical trials" (and that was two decades ago!)
What conclusions does Carlsson make?
That more attention could be focused on other neurotransmitters
