Serotonergic Agents and Alcoholism Treatment: A Simulation

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14 Scopus citations


Background: Those with early-onset alcoholism may better respond to ondansetron (a 5-HT3 receptor antagonist) than to selective serotonin reuptake inhibitor (SSRI) treatment, whereas those with late-onset alcoholism may present the reverse response pattern. Johnson and colleagues proposed a model that attempts to explain the observed treatment response patterns of those with early and late alcoholism onset by focusing on the influence of a common genetic variant in the serotonin transporter regulatory region (5-HTTLPR) on serotonin (5-HT) and dopamine (DA) system function. Methods: The present study formalizes and extends Johnson's descriptive model into a computer simulation consisting of differential equations. For each of 16 conditions defined by genotype, drinking status, diagnostic status, and drug treatment, data were generated by 100 simulation runs. Results: In every condition, the S/_genotype (S/S and S/L) had higher extracellular 5-HT levels than did the L/L genotype. The S/_genotype also had higher rates of postsynaptic DA firing than did the L/L genotype with the exception of the SSRI treatment condition, where the firing rates were similar. Drinking generally increased levels of extracellular 5-HT, reduced rates of presynaptic 5-HT firing, and increased rates of postsynaptic DA firing. Drinking produced increases in DA activation that were greater for the L/L genotype in the SSRI treatment condition and for the S/_genotype in the ondansetron treatment condition. Conclusions: Genotype at 5-HTTLPR may influence relative reward of drinking alcohol while a person is under pharmacological treatment for alcoholism. Alternatively, 5-HTTLPR genotype may influence pathways of alcohol craving. Clinical studies should examine these hypotheses.

Original languageEnglish (US)
Pages (from-to)1853-1859
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Issue number12
StatePublished - Dec 2003
Externally publishedYes


  • 5-HT Receptor
  • Computational Model
  • Ondansetron
  • SSRI
  • Serotonin Transporter

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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