title: Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?
abstract: In one of his earlier papers, Lex Cools stated that the 'concept of an impaired balance between the in series connected […] dopamine system, […] 5-HT system and […] noradrenaline system offers a single coherent and integrated theory of schizophrenia' (Cools, 1975). Since then, considerable attention has focused on the interaction between dopamine and 5-HT and it is now well accepted that most antipsychotics (especially the second-generation drugs) modulate both dopaminergic and serotonergic receptors. However, the vast majority of research has focused on the 5-HT1A, 5-HT2A and 5-HT2C receptors. In the present paper, we review the literature pertaining to the 5-HT3 receptor, the only ionotropic 5-HT receptor. We discuss both the interactions between 5-HT3 receptors and dopamine, and the animal and human literature investigating the role of 5-HT3 receptors in schizophrenia. The results show that the interactions between 5-HT3 receptors and dopamine are complex, but that 5-HT3 receptors do not have a strong influence on the positive symptoms of schizophrenia. However, when added to standard antipsychotic medication, several recent studies have found that 5-HT3 receptor antagonists can induce a statistically significantly improvement in negative and cognitive symptoms. The implications of these findings in relation to animal modelling and drug development are discussed.
authors.affiliation: aSchool of Psychology, Victoria University of Wellington, Wellington, New Zealand bRoche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Bart A
authors.initials: BA
authors.lastname: Ellenbroek
authors.forename: Eric P M
authors.initials: EP
authors.lastname: Prinssen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine