Alterations of dopamine and serotonin transmission in schizophrenia.
The present chapter outlines current thinking regarding serotonin and dopamine in schizophrenia. Each has individually been linked to theories regarding the illness' pathophysiology although the focus here is on their interactive role, a model that has driven drug development in the field for the last 10-15 years. With clozapine as a prototype, a new class of 'atypical' antipsychotics entered the clinical market, hinged predominantly on the notion that these agents were superior to conventional antipsychotics through their ratio of serotonin 5-HT(2)/dopamine D(2) binding. This model has since been challenged both clinically and theoretically, but interest in serotonin-dopamine interactions remains high in the face of a broader conceptualization of schizophrenia's symptom domains, in combination with a shift in the perceived role of dopamine vis-à-vis these different clinical features. At present, there is particular interest in the 5-HT(1A), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors as the search for improved pharmacological treatments for schizophrenia continues.
Remington
Gary
G
Department of Psychiatry, Faculty of Medicine, University of Toronto, Ontario, Canada. gary_remington@camh.net
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001519:Behavior / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000627:therapeutic use; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000502:physiology*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D004298:Dopamine