Linking animal models of psychosis to computational models of dopamine function

Andrew J. Smith, Ming Li, Suzanna Becker, Shitij Kapur

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CAR - a novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations.

Original languageEnglish (US)
Pages (from-to)54-66
Number of pages13
JournalNeuropsychopharmacology
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Computational modeling
  • Conditioned avoidance
  • Dopamine
  • Latent inhibition
  • Psychosis
  • Temporal difference learning

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Linking animal models of psychosis to computational models of dopamine function'. Together they form a unique fingerprint.

Cite this