A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency,extinction, and renewal |
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Authors: | Thomas V Wiecki Katrin Riedinger Andreas von Ameln-Mayerhofer Werner J Schmidt Michael J Frank |
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Institution: | (1) Max Planck Institute for Biological Cybernetics, Tübingen, Germany;(2) Department of Neuropharmacology, University of Tübingen, Tübingen, Germany;(3) Department of Cognitive & Linguistic Sciences, Brown University, Providence, RI, USA;(4) Department of Psychology, Brown University, Providence, RI, USA;(5) Department of Psychiatry, Brown University, Providence, RI, USA |
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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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
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Keywords: | Catalepsy Sensitization Basal ganglia D2 antagonist Haloperidol Computational models |
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