Original Investigation

Psychopharmacology

, Volume 204, Issue 2, pp 265-277

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency, extinction, and renewal

  • Thomas V. WieckiAffiliated withMax Planck Institute for Biological Cybernetics
  • , Katrin RiedingerAffiliated withDepartment of Neuropharmacology, University of Tübingen
  • , Andreas von Ameln-MayerhoferAffiliated withDepartment of Neuropharmacology, University of Tübingen
  • , Werner J. SchmidtAffiliated withDepartment of Neuropharmacology, University of Tübingen
  • , Michael J. FrankAffiliated withDepartment of Cognitive & Linguistic Sciences, Brown UniversityDepartment of Psychology, Brown UniversityDepartment of Psychiatry, Brown University Email author 

Abstract

Rationale

Repeated haloperidol treatment in rodents results in a day-to-day intensification of catalepsy (i.e., sensitization). Prior experiments suggest that this sensitization is context-dependent and resistant to extinction training.

Objectives

The aim of this study was to provide a neurobiological mechanistic explanation for these findings.

Materials and methods

We use a neurocomputational model of the basal ganglia and simulate two alternative models based on the reward prediction error and novelty hypotheses of dopamine function. We also conducted a behavioral rat experiment to adjudicate between these models. Twenty male Sprague–Dawley rats were challenged with 0.25 mg/kg haloperidol across multiple days and were subsequently tested in either a familiar or novel context.

Results

Simulation results show that catalepsy sensitization, and its context dependency, can be explained by “NoGo” learning via simulated D2 receptor antagonism in striatopallidal neurons, leading to increasingly slowed response latencies. The model further exhibits a non-extinguishable component of catalepsy sensitization due to latent NoGo representations that are prevented from being expressed, and therefore from being unlearned, during extinction. In the rat experiment, context dependency effects were not dependent on the novelty of the context, ruling out the novelty model’s account of context dependency.

Conclusions

Simulations lend insight into potential complex mechanisms leading to context-dependent catalepsy sensitization, extinction, and renewal.

Keywords

Catalepsy Sensitization Basal ganglia D2 antagonist Haloperidol Computational models