To evaluate the contribution of individual synaptic constituents, all available in vivo imaging studies on schizophrenic patients were subjected to a retrospective analysis. For the pool of
drug-naïve,
drug-free, and acutely medicated patients, major findings were increases in neostriatal
dopamine (DA) synthesis and release and decreases in neostriatal DA transporters and D1 receptors, neostriatal, thalamic, frontal, and parietal D2 receptors, mesencephalic/pontine and temporal 5-HT1A receptors, frontal and temporal HT2A and μ-amino
butyric acid (
GABA)A receptors. Based on the findings on
drug-naïve and
drug-free patients, it may be hypothesized that
schizophrenia initially is characterized by an impaired mechanism of D2
autoreceptor and heteroreceptor sensitization leading to sensitization instead of desensitization in response to increased levels of neostriatal DA.
Neuroleptic medication blocks neostriatal D2
autoreceptor and heteroreceptors, reducing neostriatal DA and disinhibiting DA action mediated by D2 heteroreceptor binding sites. Ultimately, this may result in a restitution of
GABA function, leading to a recovery of inhibitory input to the target regions of the descending corticothalamostriatal efferents. Furthermore, a blockade of inhibitory and excitatory neocortical
5-HT function may be inferred, which is likely to reduce (excitatory) DAergic input to the mesolimbic target regions of corticothalamostriatal projections.