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Pharmacopsychiatry 2011; 44: S76-S83
DOI: 10.1055/s-0031-1273697
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Bursts and the Efficacy of Selective Serotonin Reuptake Inhibitors

J. Best1 , H. F. Nijhout2 , M. Reed3
  • 1Department of Mathematics, The Ohio State University, Columbus, OH, USA
  • 2Department of Biology, Duke University, Durham, NC, USA
  • 3Department of Mathematics, Duke University, Durham, NC, USA
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Publication History

Publication Date:
05 May 2011 (online)

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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.

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Correspondence

Prof. J. Best

Department of Mathematics

The Ohio State University

Columbus, OH 43210

USA

Email: jbest@math.ohio-state.edu