Jonathan J. Chow

Isolating the incentive salience of reward-associated stimuli: value, choice, and persistence

Sign- and goal-tracking are differentially associated with drug abuse-related behavior. Recently, it has been hypothesized that sign- and goal-tracking behavior are mediated by different neurobehavioral valuation systems, including differential incentive salience attribution. Herein, we used different conditioned stimuli to preferentially elicit different response types to study the different incentive valuation characteristics of stimuli associated with sign- and goal-tracking within individuals. The results demonstrate that all stimuli used were equally effective conditioned stimuli; however, only a lever stimulus associated with sign-tracking behavior served as a robust conditioned reinforcer and was preferred over a tone associated with goal-tracking. Moreover, the incentive value attributed to the lever stimulus was capable of promoting suboptimal choice, leading to a significant reduction in reinforcers (food) earned. Furthermore, sign-tracking to a lever was more persistent than goal-tracking to a tone under omission and extinction contingencies. Finally, a conditional discrimination procedure demonstrated that sign-tracking to a lever and goal-tracking to a tone were dependent on learned stimulus-reinforcer relations. Collectively, these results suggest that the different neurobehavioral valuation processes proposed to govern sign- and goal-tracking behavior are independent but parallel processes within individuals. Examining these systems within individuals will provide a better understanding of how one system comes to dominate stimulus-reward learning, thus leading to the differential role these systems play in abuse-related behavior.

Suboptimal Choice in Pigeons: Stimulus Value Predicts Choice over Frequencies

Pigeons have shown suboptimal gambling-like behavior when preferring a stimulus that infrequently signals reliable reinforcement over alternatives that provide greater reinforcement overall. As a mechanism for this behavior, recent research proposed that the stimulus value of alternatives with more reliable signals for reinforcement will be preferred relatively independently of their frequencies. The present study tested this hypothesis using a simplified design of a Discriminative alternative that, 50% of the time, led to either a signal for 100% reinforcement or a blackout period indicative of 0% reinforcement against a Nondiscriminative alternative that always led to a signal that predicted 50% reinforcement. Pigeons showed a strong preference for the Discriminative alternative that remained despite reducing the frequency of the signal for reinforcement in subsequent phases to 25% and then 12.5%. In Experiment 2, using the original design of Experiment 1, the stimulus following choice of the Nondiscriminative alternative was increased to 75% and then to 100%. Results showed that preference for the Discriminative alternative decreased only when the signals for reinforcement for the two alternatives predicted the same probability of reinforcement. The ability of several models to predict this behavior are discussed, but the terminal link stimulus value offers the most parsimonious account of this suboptimal behavior.

Suboptimal choice in rats: Incentive salience attribution promotes maladaptive decision-making.

HighlightsIncentive salience was necessary to promote suboptimal choice.Stimuli imbued with incentive salience overshadowed primary reinforcement value.Rate of sign‐tracking was not reflective of stimulus value. ABSTRACT Stimuli that are more predictive of subsequent reward also function as better conditioned reinforcers. Moreover, stimuli attributed with incentive salience function as more robust conditioned reinforcers. Some theories have suggested that conditioned reinforcement plays an important role in promoting suboptimal choice behavior, like gambling. The present experiments examined how different stimuli, those attributed with incentive salience versus those without, can function in tandem with stimulus‐reward predictive utility to promote maladaptive decision‐making in rats. One group of rats had lights associated with goal‐tracking as the reward‐predictive stimuli and another had levers associated with sign‐tracking as the reward‐predictive stimuli. All rats were first trained on a choice procedure in which the expected value across both alternatives was equivalent but differed in their stimulus‐reward predictive utility. Next, the expected value across both alternatives was systematically changed so that the alternative with greater stimulus‐reward predictive utility was suboptimal in regard to primary reinforcement. The results demonstrate that in order to obtain suboptimal choice behavior, incentive salience alongside strong stimulus‐reward predictive utility may be necessary; thus, maladaptive decision‐making can be driven more by the value attributed to stimuli imbued with incentive salience that reliably predict a reward rather than the reward itself.

Toward isolating the role of dopamine in the acquisition of incentive salience attribution

Stimulus-reward learning has been heavily linked to the reward-prediction error learning hypothesis and dopaminergic function. However, some evidence suggests dopaminergic function may not strictly underlie reward-prediction error learning, but may be specific to incentive salience attribution. Utilizing a Pavlovian conditioned approach procedure consisting of two stimuli that were equally reward-predictive (both undergoing reward-prediction error learning) but functionally distinct in regard to incentive salience (levers that elicited sign-tracking and tones that elicited goal-tracking), we tested the differential role of D1 and D2 dopamine receptors and nucleus accumbens dopamine in the acquisition of sign- and goal-tracking behavior and their associated conditioned reinforcing value within individuals. Overall, the results revealed that both D1 and D2 inhibition disrupted performance of sign- and goal-tracking. However, D1 inhibition specifically prevented the acquisition of sign-tracking to a lever, instead promoting goal-tracking and decreasing its conditioned reinforcing value, while neither D1 nor D2 signaling was required for goal-tracking in response to a tone. Likewise, nucleus accumbens dopaminergic lesions disrupted acquisition of sign-tracking to a lever, while leaving goal-tracking in response to a tone unaffected. Collectively, these results are the first evidence of an intraindividual dissociation of dopaminergic function in incentive salience attribution from reward-prediction error learning, indicating that incentive salience, reward-prediction error, and their associated dopaminergic signaling exist within individuals and are stimulus-specific. Thus, individual differences in incentive salience attribution may be reflective of a differential balance in dopaminergic function that may bias toward the attribution of incentive salience, relative to reward-prediction error learning only.

Role of serotonin transporter function in rat orbitofrontal cortex in impulsive choice.

Impulsivity is a multi-faceted personality construct that plays a prominent role in drug abuse vulnerability. Dysregulation of 5-hydroxytryptamine (serotonin, 5-HT) systems in subregions of the prefrontal cortex has been implicated in impulsivity. Extracellular 5-HT concentrations are regulated by 5-HT transporters (SERTs), indicating that these transporters may be important molecular targets underlying individual differences in impulsivity and drug abuse vulnerability. The present study evaluated the role of SERT in mediating individual differences in impulsivity. Rats were tested for both impulsive action using the cued go/no-go task and for impulsive choice using a delay discounting task in a counterbalanced design. Following behavioral evaluation, Km and Vmax were obtained from kinetic analysis of [(3)H]5-HT uptake by SERT using synaptosomes prepared from both orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) obtained from each individual rat. Vmax for SERT in OFC, but not mPFC, was negatively correlated with mean adjusted delay scores in the delay discounting task. In contrast, Vmax for SERT in OFC and mPFC was not correlated with performance in the cued go/no-go task. To further evaluate the relationship between SERT function and impulsive choice, a selective SERT inhibitor, fluoxetine (0, 15, 50 and 150pmol/side) was microinjected bilaterally into OFC and effects on the delay discounting task determined. Following stabilization of behavior, fluoxetine increased mean adjusted delay scores (decreased impulsivity) in high impulsive rats compared to saline microinjection, but had no effect in low impulsive rats. These ex vivo and in vivo results suggest that enhanced SERT function in OFC underlies high impulsive choice behavior.

NMDA receptor blockade specifically impedes the acquisition of incentive salience attribution

&NA; Glutamatergic signaling plays an important role in learning and memory. Using Pavlovian conditioned approach procedures, the mechanisms that drive stimulus‐reward learning and memory have been investigated. However, there are instances where reward‐predictive stimuli can function beyond being solely predictive and can be attributed with “motivational value” or incentive salience. Using a Pavlovian conditioned approach procedure consisting of two different but equally predictive stimuli (lever vs. tone) we investigated the role NMDA receptor function has in the attribution of incentive salience. The results revealed that the administration of MK‐801, an NMDA receptor antagonist, during acquisition of Pavlovian conditioned approach promoted goal‐tracking to a lever stimulus, while control animals learned to sign‐track. Moreover, within the same animals, the use of a tone stimulus elicited goal‐tracking responses that were unaffected by MK‐801 pretreatments. Furthermore, a lever CS that elicited sign‐tracking served as a more robust conditioned reinforcer than a tone CS that elicited goal‐tracking or a lever CS that elicited goal‐tracking via MK‐801 pretreatments. Collectively, these results demonstrate that NMDA receptor antagonism can alter the stimulus‐reward relationship learned and prevent the attribution of incentive salience, rather than impede general learning. HighlightsNMDA receptor inhibition prevents the attribution of incentive salience.NMDA receptor inhibition promotes the acquisition of goal‐tracking.Showed within‐subject dissociation in sign‐ and goal‐tracking acquisition under MK801.

EXAMINING MEMORY CONSOLIDATION AND RECONSOLIDATION IN AN APPETITIVE PAVLOVIAN TASK

OF THESIS EXAMINING MEMORY CONSOLIDATION AND RECONSOLIDATION IN AN APPETITIVE PAVLOVIAN TASK Memory plays an important role in defining how one behaves. The neurobiological mechanisms of memory have been studied extensively in animal models and the NMDA glutamate receptor has been identified to play an important role in the consolidation and reconsolidation of appetitive memories. Certain memories, depending on what was learned, can function differently and can be more difficult to disrupt based on a number of factors. Currently, no study has examined whether or not a rewardpredictive stimulus attributed with incentive value is more difficult to disrupt than a stimulus that functions as a general reward-predictor. To determine the role of the NMDA receptor on memory consolidation with different functioning reward-predictive stimuli rats underwent a Pavlovian conditioned approach, where a post-session NMDA receptor antagonist was administered daily. Furthermore, to determine the role of the NMDA receptor on memory reconsolidation, another set of rats were trained on a Pavlovian conditioned approach task, after training was complete rats were presented with a reward-predictive stimuli followed by an administration of a NMDA receptor antagonist and then re-tested.