Serotonin-dopamine interaction and its relevance to schizophrenia.
OBJECTIVE
The therapeutic success of clozapine and risperidone has focused attention on the interaction between serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance.


METHODS
The authors synthesized information from more than 100 published articles obtained through electronic and bibliography-directed searches.


RESULTS
The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symptoms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with doses that produce suprathreshold dopaminergic blockade.


CONCLUSIONS
Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.
Kapur
S
S
Clarke Institute of Psychiatry, Toronto, Ont., Canada.
Remington
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D008636:Mesencephalon / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use
D014150:Antipsychotic Agents; D015259:Dopamine Agents; D018490:Serotonin Agents; D012701:Serotonin; D003024:Clozapine; D018967:Risperidone; D004298:Dopamine