Document Detail

A neurocomputational account of catalepsy sensitization induced by D2 receptor blockade in rats: context dependency, extinction, and renewal.
MedLine Citation:
PMID:  19169674     Owner:  NLM     Status:  MEDLINE    
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.
Thomas V Wiecki; Katrin Riedinger; Andreas von Ameln-Mayerhofer; Werner J Schmidt; Michael J Frank
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-01-24
Journal Detail:
Title:  Psychopharmacology     Volume:  204     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-04-28     Completed Date:  2009-08-05     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  265-77     Citation Subset:  IM    
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MeSH Terms
Basal Ganglia / drug effects
Behavior, Animal / drug effects
Catalepsy / chemically induced,  psychology*
Computer Simulation
Dopamine Antagonists*
Extinction, Psychological / drug effects*
Models, Neurological
Rats, Sprague-Dawley
Receptors, Dopamine D2 / antagonists & inhibitors*
Grant Support
R01 MH080066/MH/NIMH NIH HHS; R01 MH080066-01/MH/NIMH NIH HHS; R01 MH080066-01A1/MH/NIMH NIH HHS
Reg. No./Substance:
0/Dopamine Antagonists; 0/Receptors, Dopamine D2; J6292F8L3D/Haloperidol

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