title: Bursts and the efficacy of selective serotonin reuptake inhibitors.
abstract: We present a new hypothesis for the efficacy of selective serotonin reuptake inhibitors (SSRIs). We propose that SSRIs bring the response to the phasic firing of raphe nucleus cells back to normal, even though the average extracellular 5HT concentration remains low. We discuss burst firing in the raphe nuclei and use mathematical models to argue that tonic firing and phasic firing may be decoupled and may come from different mechanisms. We use a mathematical model for serotonin synthesis, release, and reuptake in terminals to illustrate the responses in terminal regions to bursts in a normal individual and in an individual with low vesicular serotonin. We then show that acute doses of SSRIs do not bring the response to bursts back to normal, but that chronic doses do return the response to normal. These model results need to be confirmed by new electrophysiological and pharmacological experiments.
authors.affiliation: Department of Mathematics, The Ohio State University, Columbus, OH 43210, USA. jbest@math.ohio-state.edu
authors.forename: J
authors.initials: J
authors.lastname: Best
authors.forename: H F
authors.initials: HF
authors.lastname: Nijhout
authors.forename: M
authors.initials: M
authors.lastname: Reed
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008962:Models, Theoretical; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors