Disruption of model-based behavior and learning by cocaine self-administration in rats.
BACKGROUND
Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis.


OBJECTIVE
This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment.


METHODS
We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes.


RESULTS
Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward.


CONCLUSIONS
These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.
Cellular Neurobiology Research Branch, Behavioral Neurophysiology Research Section, National Institute on Drug Abuse Intramural Research Program, 251 Bayview Blvd., Baltimore, MD, 21224, USA.
Heather M
HM
Wied
Joshua L
JL
Jones
Nisha K
NK
Cooch
Benjamin A
BA
Berg
Geoffrey
G
Schoenbaum
D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration
D003042:Cocaine