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


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


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.
Wiecki
Thomas V
TV
Max Planck Institute for Biological Cybernetics, Tübingen, Germany. thomas.wiecki@tuebingen.mpg.de
Riedinger
Katrin
K
von Ameln-Mayerhofer
Andreas
A
Schmidt
Werner J
WJ
Frank
Michael J
MJ
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology*; D003198:Computer Simulation; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D005108:Extinction, Psychological / Q000187:drug effects*; D006220:Haloperidol; D008297:Male; D008959:Models, Neurological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol