Antipsychotics - DA Hypothesis of Schizophrenia Flashcards
Describe the nigrostriatal DA pathway.
Contains DA neurons whose cell bodies reside in the substantia nigra and project to the dorsal striatum of the basal ganglia, which contains the cuadate nucleus and the putamen. This DA system is important for the integration of smooth movements (it is the extrapyramidal motor system).
What happens when there is a deficiency of DA at synapses in the nigrostriatal pathway?
Symptoms that resemble those of Parkinson’s disease: tremors, slowed motor functions, stiff limbs, and trouble maintaining balance.
These are called Extrapyramidal signs and symptoms (EPS).
How do antipsychotic medications produce EPS?
Blocking the activity of dopamine in the nigrostriatal pathway. Often makes the medications intolerable.
What other two DA pathways are indicated in schizophrenia development?
Mesocortical pathway and the mesolimbic pathway.
Describe the mesocortical pathway.
Cell bodies that reside in the VTA and send projections to release DA in the cortex.
Describe the mesolimbic pathway.
Nucleus accumbens and limbic structures, including the hippocampus and amygdala.
What is the basic tenet of the DA hypothesis?
That schizophrenia and other psychoses result from excessive dopamine activity in the brain.
What are the main supports for the DA hypothesis?
a) Drugs that increase DA function (e.g. cocaine or amphetamine) can, in high doses or with chronic administration, produce a state almost indistinguishable from the positive symptoms of schizophrenia.
b) the antipsychotics available at the time (i.e the typicals) were all DA antagonists.
Describe the correlation between the therapeutic dose and affinity for DA receptors of antipsychotics.
the correlation between the therapeutic dose of a typical antipsychotic and the drug’s affinity for the DA re eptor was found to be almost perfect.
The weaker the drug’s affinity for the DA receptor the larger the dose required to produce a therapeatic effect.
Which DA receptor is involved in schizophrenia?
Excessive DA activity at D2 receptors. The most effective antipsychotics are those with high affinity for D2 receptors.
