Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation

Abstract

An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

Figure 1.

Diagram showing the trial structure of the rGT. The task began with illumination of the tray light. A nose-poke response in the food tray initiated a new trial. After an ITI of 5 s, 4 stimulus lights were turned on in holes 1, 2, 4, and 5, and the animal was required to respond in 1 of these holes within 10 s. This response was then rewarded or punished depending on the reinforcement schedule for that option. The p values refer to the probability of a trial resulting in reward or a punishing time-out period. The reward magnitude or duration of the time-out period is indicated beside each option. If the animal was rewarded, the stimulus lights were extinguished and the animal received the corresponding number of pellets in the now-illuminated food tray. If the animal was punished, the stimulus light in the corresponding hole flashed at a frequency of 0.5 Hz for the duration of the time-out period and all other lights were extinguished. Failure to respond at the illuminated holes resulted in an omission, whereas a response during the ITI was classified as a premature response and punished by a 5 s time-out during which the house light was turned on. 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 2-pellet option, P2, is the best option. Figure is modified from Zeeb et al. (2009) and Zeeb and Winstanley (2011).

Figure 2.

Extent of lesion in the OFC or BLA. The extent of damage to the largest (light gray) and smallest (dark gray) regions of the OFC (left) and BLA (right), regardless of hemisphere, are depicted schematically on the right hemisphere. DLO indicates dorsolateral prefrontal cortex; IL, infralimbic cortex; LO, lateral orbitofrontal cortex; MO, medial orbitofrontal cortex; PrL, prelimbic cortex; VO, ventral orbitofrontal cortex.

Figure 3.

Acquisition and performance of the rGT. A, Animals in the sham-control group chose the best option, P2, the most (compared with the other three options), an effect that increased with further training. Whereas their choice of P1 declined with each training session, the animals' choice of the disadvantageous options (P3 and P4) remained relatively low throughout training. A similar effect was observed in the unilateral lesion group (B). C, Animals with ipsilateral lesions had a harder time distinguishing between the best two options during the first few training days, although this behavior was not significantly different from the sham-control group. D, Rats with contralateral lesions initially preferred P1, the second-best option. These rats were also significantly slower than sham-control animals in learning the optimal strategy (choosing most often from P2). E, After training on the rGT, there were no significant differences in choice preferences between the four groups. Data are represented as the mean percentage choice of each option ± SEM.

Figure 4.

Effects of acute food satiety on choice preferences. A, B, Sham-control rats (A) and animals with unilateral lesions (B) changed their choice pattern in response to SSS and SSS-Ext. Both groups of rats showed an increased choice of P1 and a decreased choice of P2. C, Rats with ipsilateral lesions significantly changed their choice preferences after SSS and SSS-Ext; however, the change in behavior during extinction was not as drastic as that observed in the other two groups. D, A contralateral lesion of the OFC and BLA prevented animals from updating their choice behavior in response to all acute satiety manipulations. Data are represented as the mean percentage choice of each option ± SEM. *p ≤ 0.05 for significant difference from the group's own baseline according to a paired-sample t test; ^#p = 0.05–0.07.

Figure 5.

Change in the number of trials completed after acute satiety manipulations. A decreased number of trials completed was observed in all groups after each satiety day. However, animals with contralateral lesions showed the least change in the number of trials completed after SSS and SSS-Ext. However, this effect was only significantly different from the sham-control rats during SSS. Data are represented as mean ± SEM.

Figure 6.

Effects of chronic food satiety on rGT performance. Compared with baseline (BL), satiation with regular chow did not drastically affect choice behavior in any group. A, B, Sham-control rats chose P2 slightly less on the first day of chronic feeding (A), whereas a similar effect was observed for rats with unilateral lesions on the second chronic feeding day (B). C, D, There was no significant effect of chronic feeding in either the ipsilateral (C) or contralateral (D) lesion rats; however, visual inspection of the data indicated that a similar effect (decreased choice of P2) was initially observed. Data are represented as the mean percentage choice of each option ± SEM.

Figure 7.

Difference in the number of trials completed from baseline after chronic food satiety. Rats in all groups showed a similar decrease in the number of trials completed compared with baseline after chronic food satiety. This effect did not significantly differ between groups, although visual inspection of the data indicated that the smallest decrease in the number of trials completed was observed in the contralateral lesion group. Data are represented as mean ± SEM.