The complexity of the dopaminergic synapses and their modulation by antipsychotics

Since the mid of the 1960s, striking similarities between the psychosis seen in subjects taking high doses of amphetamines and the symptoms of patients with paranoid schizophrenia have been noted and placed in the context of increased catecholaminergic neurotransmission as a fundamental cause underlying major symptoms of the disease. Subsequent studies emphasized the contribution of central dopaminergic mechanisms for at least several psychotic symptoms of schizophrenia. The most compelling pharmacological data to support the developing "dopamine hypothesis of schizophrenia" originated from the clear relationship between antipsychotic drug efficacy and affinity for D2-like dopamine receptors strongly indicating D2-antagonism as major if not exclusive mechanism of antipsychotic drug action. Accordingly, in this review we focus on the neuropharmacology of the dopaminergic system in our brain with special emphasis on the dopaminergic synapse.