ABSTRACT
This chapter first examines version 1 of the dopamine hypothesis that excessively active dopamine transmission precipitates schizophrenia symptoms. Following new evidence, version 2 proposed that overactivity of dopamine D2 receptor neurotransmission in the subcortical and limbic brain regions contributes to aberrant salience manifesting itself in positive symptoms of schizophrenia. Negative and cognitive symptoms were attributed to underactive dopamine D1 receptor neurotransmission in the prefrontal cortex. Version 3 proposed that environmental stress and substance abuse interact with genetic susceptibility, causing dopamine dysregulation. Increases in striatal presynaptic dopamine concentration cause psychosis through aberrant salience to external stimuli. Further revisions are underway. Dissenters criticise dopamine hypotheses ineffectually. Claims that the original hypothesis is still current overlooks its continuing development. Calling it simplistic and unsubstantiated is outdated. Saying researchers have continually failed to confirm the original hypothesis misunderstands how hypotheses develop. Claiming after such ‘failure,’ researchers turned to other neurochemicals mis-sequences events. Stating that most researchers envisage a chemical solution to schizophrenia assumes they deny environmental factors. Claims that failed neurochemical explanations indicate avoiding antipsychotics, undermining drug company marketing, overlooks that dopamine hypotheses have developed as has the understanding of drug action on neurochemicals.
