ABSTRACT
I. Introduction .............................................................................................................................31 II. Mesotelencephalic Dopamine Systems ..................................................................................32 III. Biochemical Pharmacology of Dopamine Neurons ...............................................................32 IV. Effects of Typical Antipsychotic Drugs on Mesotelencephalic Dopamine Systems ............33 V. Effects of Atypical Antipsychotic Drugs on Mesotelencephalic Dopamine Systems...........34 VI. Antipsychotic Drug Effects in an Animal Model of Schizophrenia......................................35 VII. An Hypothesis for Atypical Antipsychotic Drug Action .......................................................37 References ........................................................................................................................................37
The antagonism of central dopamine receptors by antipsychotic drugs has been postulated as a critical determinant of the therapeutic efficacy of this class of drugs. It is clear, however, that drugs with clinically antipsychotic effects influence dopamine transmission at several levels, including transmitter synthesis, release, and metabolism. Indeed, the “dopamine hypothesis” of schizophrenia was originally offered based upon studies of the alterations in brain dopamine metabolism produced by haloperidol and chlorpromazine in mice.
