Neurotransmisson of dopamin and serotonin

In a dissertation presented at KI on february 23, Yua-Hwa Chou uses the brain imagin technique PET to study dopamine and serotonin neurotransmission.

In schizophrenia research, an important observation is that patients with schizophrenia, when compared with controls, have higher amphetamine induced dopamine release in the striatum. An aim of the thesis project was to develop methods for measurement of endogenous dopamine levels in brain areas that are of central interest in schizophrenia research. The investigations were conducted on primates.

The overall aim was to examine the effecy of endogenous dopamine and the portotype atypic antipsychotic drug clozapine on readioligand binding to dopamine and serotonin receptors in the primate brain.

Clozapin, is a neurolepticum that is commonly used in the treatment of schizophrenia when attampts of using other chemically related types of neuroleptics have failed and forced to stop due to too serious neurological side effects. A second aim of the study was to examine the possible mechanisms underlying the atypical properties of clozapin.

Previous studies of clozapine suggest a ceiling effect for the drug. However, Chou´s research indicate that clozapine saturates striatal D2/D3 dopamin receptors at high doses. This finding do not support the hypothesis of a ceiling effect.

D1-like dopamine receptor occupancy by clozapine may be higher in the frontal cortex than in the striatum. This finding supports the view that the D1-like dopamine receptors in the frontal cortex may mediate clozapine´s action.

Another finding by Chou suggests that the 5-HT1A receptor is a candidate target for the drug action of clozapine.

Read an abstract of the dissertation