A computational hypothesis for allostasis: Delineation of substance dependence, conventional therapies, and alternative treatments

Yariv Z. Levy, Dino J. Levy, Andrew G. Barto, Jerrold S. Meyer

Research output: Contribution to journalArticlepeer-review


The allostatic theory of drug abuse describes the brain's reward system alterations as substance misuse progresses. Neural adaptations arising from the reward system itself and from the antireward system provide the subject with functional stability, while affecting the person's mood. We propose a computational hypothesis describing how a virtual subject's drug consumption, cognitive substrate, and mood interface with reward and antireward systems. Reward system adaptations are assumed interrelated with the ongoing neural activity defining behavior toward drug intake, including activity in the nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC). Antireward system adaptations are assumed to mutually connect with higher-order cognitive processes occurring within PFC, orbitofrontal cortex, and anterior cingulate cortex. The subject's mood estimation is a provisional function of reward components. The presented knowledge repository model incorporates pharmacokinetic, pharmacodynamic, neuropsychological, cognitive, and behavioral components. Patterns of tobacco smoking exemplify the framework's predictive properties: escalation of cigarette consumption, conventional treatments similar to nicotine patches, and alternative medical practices comparable to meditation. The primary outcomes include an estimate of the virtual subject's mood and the daily account of drug intakes. The main limitation of this study resides in the 21 time-dependent processes which partially describe the complex phenomena of drug addiction and involve a large number of parameters which may underconstrain the framework. Our model predicts that reward system adaptations account for mood stabilization, whereas antireward system adaptations delineate mood improvement and reduction in drug consumption. This investigation provides formal arguments encouraging current rehabilitation therapies to include meditation-like practices along with pharmaceutical drugs and behavioral counseling.

Original languageEnglish
Article numberArticle 167
JournalFrontiers in Psychiatry
Issue numberDEC
StatePublished - 2013


  • Allostasis
  • Antireward system adaptations
  • Drug addition
  • Drug intake prediction
  • Knowledge repository model
  • Mood
  • Multiscale computational model
  • Reward system adaptations

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health


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