Disruption of model-based behavior and learning by cocaine self-administration in rats

Abstract

Rationale: 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.

Objectives: 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.

Fig. 1

Rats were trained to press the active lever to self-administer a 10 % liquid sucrose solution or cocaine–HCl (0.75 mg/kg/infusion). Figures show the mean number of lever presses on the active and passive levers for sucrose controls (a) and cocaine rats (b) over 14 days. The mean number of sucrose or cocaine reward deliveries during each session is also shown. Error bars = SEM

Fig. 2

Cocaine self-administration disrupts the expression of behavior that depends upon inferred values. The experimental timeline is schematized at the bottom of the figure. Figures show the percentage of time spent in food cup during presentation of the cues during each of the three phases of training: preconditioning (a, b), conditioning (c, d), and the probe test (e, f). Control rats are presented in the top panels (a, c, e) and the cocaine-experienced rats are shown in the bottom panels (b, d, f). *p<0.05, **p<0.01 or better. Error bars = SEM

Fig. 3

Cocaine self-administration disrupts learning that depends upon inferred values. The experimental timeline is schematized at the bottom of the figure. Figures show the percentage of time spent in food cup during presentation of the cues during blocking conditioning (a, b) and the subsequent probe test (c, d). Control rats are presented in the top panels (a, c) and the cocaine-experienced rats are shown in the bottom panels (b, d). **p<0.01 or better. Error bars = SEM