Lesions of the basolateral amygdala and orbitofrontal cortex differentially affect acquisition and performance of a rodent gambling task

Abstract

Risky decision making on the Iowa Gambling Task (IGT) has been observed in several psychiatric disorders, including substance abuse, schizophrenia, and pathological gambling. Such deficits are often attributed to impaired processing within the orbitofrontal cortex (OFC) because patients with damage to this area or to the amygdala, which is strongly interconnected with the OFC, can likewise show enhanced choice of high-risk options. However, whether damage to the OFC or amygdala impairs subjects' ability to learn the task, or actually affects the decision-making process itself, is currently unclear. To address these issues, rats were trained to perform a rodent gambling task (rGT) either before or after bilateral excitotoxic lesions to the basolateral amygdala (BLA) or OFC. Maximum profits in both the rGT and IGT are obtained by favoring smaller rewards associated with lower penalties, and avoiding the tempting, yet ultimately disadvantageous, large reward options. Lesions of the OFC or BLA made before task acquisition initially impaired animals' ability to determine the optimal strategy, but did not disrupt decision making in the long term. In contrast, lesions of the BLA, but not the OFC, made after the task had been acquired increased risky choice. These results suggest that, although both regions contribute to the development of appropriate choice behavior under risk, the BLA maintains a more fundamental role in guiding these decisions. The maladaptive choice pattern observed on the IGT in patients with OFC lesions could therefore partially reflect a learning deficit, whereas amygdala damage may give rise to a more robust decision-making impairment.

Figure 1.

Experimental timeline and rGT schematic. A, Timeline indicating when rGT training occurred and when lesion or sham surgery was performed in the two groups. B, Trial structure of the rGT. The p values refer to the probability of a trial resulting in reward or a punishing time-out period. The magnitude of the reward or duration of the time-out period is indicated beside each option. The maximum numbers of pellets that could be obtained if an animal chose a single option exclusively within a single session, assuming each trial lasted 5 s, are listed at the bottom of the diagram, indicating that the two-pellet option, P2, is the best option (schematic modified from Zeeb et al., 2009).

Figure 2.

Location and extent of excitotoxic lesions. A–D, Photomicrographs of sham control (A, B) and typical BLA and OFC lesion (C, D) tissue, stained with cresyl violet. E, F, An illustration outlining the boundaries of the largest (gray) and smallest (black) area affected in any one section are shown for both the BLA (E) and OFC (F) lesion groups. Numbers beside each section in E and F correspond to the distance from bregma in millimeters. AI, Agranular insular cortex; AIV, agranular insular cortex ventral part; amygdala; CeA, central amygdala; DLO, dorsolateral prefrontal cortex; IL, infralimbic cortex; LO, lateral orbitofrontal cortex; MO, medial orbitofrontal cortex; PrL, prelimbic cortex; VO, ventral orbitofrontal cortex.

Figure 3.

Acquisition of the rGT. A, Animals with sham lesions showed a rapid increase in choice of the two-pellet option, P2, during the first five free-choice training sessions, while subsequently decreasing choice of the less advantageous options. B, C, In contrast, animals with BLA (B) or OFC (C) lesions were slower to learn the rGT, choosing P1 more often and P2 less often during the initial training stages compared with sham-operated control rats. These data indicate that determining the best option appears to be more difficult for both lesion groups during task acquisition.

Figure 4.

Choice patterns of rats with BLA or OFC lesions. A–C, Once training had been completed (30–35 postoperative free-choice sessions), rats with pretraining lesions of the BLA chose advantageously, and did not differ from sham-operated control rats in their overall choice (A), discrimination between the good and bad options (B), or choice score (C). D–F, In contrast, rats which received BLA lesions following rGT training chose the disadvantageously (D, E), resulting in a significantly lower choice score (F) compared with sham-operated controls. In contrast, rats with either pretraining or posttraining OFC lesions did not differ from sham-operated rats. Data are expressed as the mean ± SEM. of the last three stable postoperative sessions. Asterisk (*) indicates a significant difference (p < 0.05) determined by a two-sample t test comparing the BLA lesion group to the sham-operated control group.