1. ¹Bentley Heath, Solihull, West Midlands, UK
2. ²Department of Psychology, University of Nebraska-Lincoln, Lincoln, NE, USA
3. ³Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, ON, Canada
4. ⁴Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

Correspondence: Dr S Kapur, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada. E-mail: andys_kathmandu@yahoo.com

Received 30 September 2005; Revised 8 March 2006; Accepted 9 March 2006; Published online 10 May 2006.

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.