Impaired flexibility in decision making in rats after administration of the pharmacological stressor yohimbine

Abstract

Rationale: Stress-induced disruption of decision making has been hypothesized to contribute to drug-seeking behaviors and addiction. Noradrenergic signaling plays a central role in mediating stress responses. However, the effects of acute stress on decision making, and the role of noradrenergic signaling in regulating these effects, have not been well characterized.

Objective: To characterize changes in decision making caused by acute pharmacological stress, the effects of yohimbine (an α2-adrenergic antagonist) were examined in a delay discounting task. Noradrenergic contributions to decision making were further characterized by examining the effects of propranolol (a β antagonist), prazosin (an α1 antagonist), and guanfacine (an α2 agonist).

Methods: Sprague-Dawley rats were administered drugs prior to performance on a delay discounting task, in which the delay preceding the large reward increased within each session (ascending delays). To dissociate drug-induced changes in delay sensitivity from behavioral inflexibility, drug effects were subsequently tested in a modified version of the discounting task, in which the delay preceding the large reward decreased within each session (descending delays).

Results: Yohimbine increased choice of the large reward when tested with ascending delays but decreased choice of the same large reward when tested with descending delays, suggesting that drug effects could be attributed to perseverative choice of the lever preferred at the beginning of the session. Propranolol increased choice of the large reward when tested with ascending delays. Prazosin and guanfacine had no effect on reward choice.

Conclusions: The stress-like effects of yohimbine administration may impair decision making by causing inflexible, perseverative behavior.

Figure 1

Behavioral paradigms. Delay discounting tasks with a ascending and b descending delay order

Figure 2

a Effect of yohimbine on preference for the large reward in the ascending delays task, b Effect of yohimbine on preference for the large reward in the descending delays task. * denotes significance vs. vehicle administration (p < 0.01). Graph symbols show mean preference ± SEM

Figure 3

Long-lasting yohimbine effects, a Preference for the large reward in the ascending delays discounting task, b Preference for the large reward in the descending delays task on the day preceding yohimbine administration, c Effect of acute administration of yohimbine on reward preference in the descending delays task, d–f Yohimbine administration had long-lasting effects on choice behavior in a subset of rats when tested in subsequent drug-free sessions, g Delay discounting behavior after extensive retraining in the descending delays task. * denotes significance vs. pre-yohimbine preference within a specific block (p < 0.01). Symbols indicate mean preference ± SEM

Figure 4

a Effect of propranolol on preference for large rewards in the ascending delays task, b Effect of propranolol on preference for large rewards in the descending delays task. * denotes significance for 10 mg/kg propranolol vs vehicle (p < 0.05). Symbols indicate mean preference ± SEM

Figure 5

a Effect of prazosin on preference for the large reward in the ascending delays task, b Effect of guanfacine on preference for the large reward in the ascending delay task. Symbols indicate mean preference ± SEM