The dopamine hypothesis states that the symptoms of schizophrenia are related to increased dopaminergic neurotransmission. Positron Emission Tomography (PET) has so far been used to examine dopamine receptors in the striatum which is a large brain region with high receptor density. The amygdala, thalamus, n. accumbens, s. nigra and several cortical areas are extrastriatal regions of central interest in schizophrenia research. However, the low density of D2-dopamine receptors in these regions has precluded quantitative PET-studies. A new high resolution PET-system and a new radioligand ([11C]FLB 457) with very high affinity for D2-dopamine receptors (20pM) will now be used for quantitative determination of receptor binding in extrastriatal brain regions of patients with schizophrenia. Several observations indicate laterality in brain morphology and brain function of patients with schizophrenia. We have previously demonstrated laterality in striatal D2-dopamine receptor density. Lateral brain asymmetry of dopamine receptor binding will now be examined not only in the striatum but also in the amygdala, thalamus, n.accumbens, s. nigra and throughout all cortical areas. There is increasing support for the hypothesis that the antipsychotic effect of neuroleptic drugs is mediated in cortical brain regions. The atypical antipsychotic clozapine has in experimental studies been shown to have preferential effect on limbic and cortical dopaminergic neurotransmission. Using PET a high dopamine receptor occupancy has been demonstrated in the striatum of antipsychotic drug treated patients. In search for regions that mediate the antipsychotic effect we will now examine dopamine receptor occupancy in cortical and limbic brain regions of patients treated with classical neuroleptics and clozapine.
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