Reward Motivation Research Articles

Maternal neglect alters reward-anticipatory behavior, social status stability, and reward circuit activation in adult male rats.

Adverse early life experiences affect neuronal growth and maturation of reward circuits that modify behavior under reward predicting conditions. Previous studies demonstrate that rats undergoing denial of expected reward in the form of maternal contact (DER-animal model of maternal neglect) during early post-natal life developed anhedonia, aggressive play-fight behaviors and aberrant prefrontal cortex structure and neurochemistry. Although many studies revealed social deficiency following early-life stress most reports focus on individual animal tasks. Thus, attention needs to be given on the social effects during group tasks in animals afflicted by early life adversity. To investigate the potential impact of the DER experience on the manifestation of behavioral responses induced by natural rewards, we evaluated: 1) naïve adult male sexual preference and performance, and 2) anticipatory behavior during a group 2-phase food anticipation learning task composed of a context-dependent and a cue-dependent learning period. DER rats efficiently spent time in the vicinity of and initiated sexual intercourse with receptive females suggesting an intact sexual reward motivation and consummation. Interestingly, during the context-dependent phase of food anticipation training DER rats displayed a modified exploratory activity and lower overall reward-context association. Moreover, during the cue-dependent phase DER rats displayed a mild deficit in context-reward association while increased cue-dependent locomotion. Additionally, DER rats displayed unstable food access priority following food presentation. These abnormal behaviours were accompanied by overactivation of the ventral prefrontal cortex and nucleus accumbens, as assessed by pCREB levels. Collectively, these data show that the neonatal DER experience resulted in adulthood in altered activation of the reward circuitry, interfered with the normal formation of context-reward associations, and disrupted normal reward access hierarchy formation. These findings provide additional evidence to the deleterious effects of early life adversity on reward system, social hierarchy formation, and brain function.

Reward motivation adaptation in people with negative schizotypal features: development of a novel behavioural paradigm and identifying its neural correlates using resting-state functional connectivity analysis.

Reward motivation in individuals with high levels of negative schizotypal traits (NS) has been found to be lower than that in their counterparts. But it is unclear that whether their reward motivation adaptively changes with external effort-reward ratio, and what resting-state functional connectivity (rsFC) is associated with this change. Thirty-five individuals with high levels of NS and 44 individuals with low levels of NS were recruited. A 3T resting-state functional brain scan and a novel reward motivation adaptation behavioural task were administrated in all participants. The behavioural task was manipulated with three conditions (effort > reward condition vs. effort < reward condition vs. effort = reward condition). Under each condition were rated 'wanting' and 'liking' for rewards. The seed-based voxel-wise rsFC analysis was conducted to explore the rsFCs associated with the 'wanting' and 'liking' ratings in individuals with high levels of NS. 'Wanting' and 'liking' ratings of individuals with high levels of NS significantly declined in the effort > reward condition but did not rebound as high as their counterparts in the effort < reward condition. The rsFCs in NS group associated with these ratings were altered. The altered rsFCs in NS group involved regions in the prefrontal lobe, dopaminergic brain regions (ventral tegmental area, substantia nigra), hippocampus, thalamus and cerebellum. Individuals with high levels of NS manifested their reward motivation adaptation impairment as a failure of adjustment adaptively during effort-reward imbalance condition and altered rsFCs in prefrontal, dopaminergic and other brain regions.

The prediction of effort-reward imbalance for reward motivation.

This sequential mediation analysis study examined how the baseline effort-reward imbalance (ERI) would predict reward motivation 1 year later in 435 college students. We found that negative/disorganized schizotypal traits and anticipatory pleasure experience together mediate the prediction of ERI for reward motivation.

Deficits in consummatory reward relate to severity of cocaine use

Background and aimsIdentifying modifiable neuropsychological factors associated with more severe CUD could improve CUD treatment. Impairments in processing of non-drug rewards may be one such factor. This study assessed the relationship between reward functioning and cocaine use severity using multi-modal measures of three distinct reward functions: consummatory reward (pleasure or “liking”); motivational reward (“wanting”) and reward learning. MethodsFifty-three adults with at least moderate CUD completed self-report and behavioral measures of consummatory reward, motivational reward and reward learning, and a composite cocaine use severity measure including quantity, frequency and life impacts of cocaine use. We conducted parallel Frequentist and Bayesian multiple regressions with measures of reward functioning as predictors of cocaine use severity. ResultsLess self-reported ability to experience pleasure, a hypothesized measure of consummatory reward, significantly predicted greater severity after adjustment for covariates and multiple hypothesis testing, β = 0.39, t(38) = 2.86, p = 0.007. Bayesian analyses confirmed a highly likely association between severity and ability to experience pleasure, and provided moderate evidence for associations with willingness to exert effort and reward learning. ConclusionsOur results suggest that less experience of subjective pleasure is related to greater cocaine use severity. This cross-sectional study cannot establish whether differences in consummatory reward are pre-existing, a result of CUD, or both. However, these results suggest interventions focused on increasing subjective pleasure, such as mindful “savoring”, should be investigated for CUD.

Exogenous oxytocin microinjection into the nucleus accumbens shell attenuates social dominance in group-housed male mice

The nucleus accumbens (NAc), a part of the brain's limbic system, is involved in a variety of brain functions, including reward motivation and social hierarchy. Here, the study investigated the effect of intra-NAc different subregions microinjections of oxytocin on social hierarchy regulation. The hierarchical ranking of group-housed male mice in laboratory settings was determined through the tube test, and a new reliable and robust behavior assay—the mate competition test—was proposed. The mice were randomly divided into two groups, and the bilateral guide cannula was implanted into the shell and core of the NAc, respectively. After social dominance stabilized, changes in social hierarchy were determined through the tube test, warm spot, and mate competition tests. Intra-NAc shell microinjections of oxytocin (0.5 μg/site), but not the core (0.5 μg/site), significantly reduced the social dominance of mice. In addition, oxytocin microinjection into both the shell and core of the NAc significantly increased locomotor ability without affecting anxious behaviors. These findings are tremendously important in understanding the functions of the NAc subregions for social dominance and are more likely to indicate the potential of an oxytocin therapeutic strategy for psychiatric disorders and social impairments.

0229 Reward motivation improves placekeeping performance after total sleep deprivation and a night of rest

Abstract Introduction Sleep deprivation impairs some higher-order cognitive processes, but it is unclear if this reflects impaired ability to perform complex tasks, a reduction in motivation, or both. There is evidence that reward motivation attenuates the effect of sleep deprivation on lower-level cognitive processes, namely vigilant attention. We investigated the extent to which reward motivation would mitigate the effect of sleep deprivation on placekeeping, a higher-order cognitive process that plays a central role in accurate performance of procedural tasks. To conduct the study under pandemic conditions, we developed a novel method to conduct sleep deprivation research remotely. Methods Participants (N = 414) joined a Zoom meeting in the evening and completed the Psychomotor Vigilance Task (PVT) and a placekeeping task (UNRAVEL). At 00:00, we randomly assigned participants to stay awake in the meeting overnight (Deprivation) or leave the meeting and sleep (Rested). Two trained researchers stayed in the meeting overnight to monitor participants. At 08:30, Rested participants re-joined the meeting, and all participants completed the PVT and UNRAVEL again. Some participants (Motivated), but not others (Nonmotivated), could earn a monetary reward based on their morning UNRAVEL accuracy. Performance on the PVT was completed before the motivation manipulation. Results We examined morning UNRAVEL accuracy using a 2 (Sleep: Deprivation, Rested) x 2 (Reward: Motivated, Nonmotivated) between-participants design with evening performance as a covariate. Deprivation participants made more errors than Rested participants, Motivated participants made fewer errors than Nonmotivated participants, and there was no interaction between the factors. Conclusion Motivational interventions may be an effective way to mitigate some of the effects of sleep deprivation on higher-order cognitive tasks. However, reward motivation affected Deprivation and Rested participants similarly, and, therefore, did not compensate for impairments specific to sleep deprivation. Consistent with results of studies testing effects of naps and caffeine, the present results suggest that sleep deprivation impairs the ability to perform a procedural sequence accurately in a way that is difficult to mitigate. Support (if any) This work was funded by the Office of Naval Research (N00014-20-1-2739).

Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.

Dopamine (DA) is a catecholamine neurotransmitter widely distributed in the central nervous system. It participates in various physiological functions, such as feeding, anxiety, fear, sleeping and arousal. The regulation of feeding is exceptionally complex, involving energy homeostasis and reward motivation. The reward system comprises the ventral tegmental area (VTA), nucleus accumbens (NAc), hypothalamus, and limbic system. This paper illustrates the detailed mechanisms of eight typical orexigenic and anorexic neuropeptides that regulate food intake through the reward system. According to recent literature, neuropeptides released from the hypothalamus and other brain regions regulate reward feeding predominantly through dopaminergic neurons projecting from the VTA to the NAc. In addition, their effect on the dopaminergic system is mediated by the prefrontal cortex, paraventricular thalamus, laterodorsal tegmental area, amygdala, and complex neural circuits. Research on neuropeptides involved in reward feeding can help identify more targets to treat diseases with metabolic disorders, such as obesity.

Neurobehavioral Reward and Sleep-Circadian Profiles Predict Present and Next-Year Mania/Hypomania Symptoms

BackgroundHeightened reward sensitivity/impulsivity, related neural activity, and sleep-circadian disruption are important risk factors for bipolar spectrum disorders, the defining feature of which is mania/hypomania. Our goal was to identify neurobehavioral profiles based on reward and sleep-circadian features and examine their specificity to mania/hypomania versus depression vulnerability. MethodsAt baseline, a transdiagnostic sample of 324 adults (18–25 years) completed trait measures of reward sensitivity (Behavioral Activation Scale), impulsivity (UPPS-P-Negative Urgency), and a functional magnetic resonance imaging card-guessing reward task (left ventrolateral prefrontal activity to reward expectancy, a neural correlate of reward motivation and impulsivity, was extracted). At baseline, 6-month follow-up, and 12-month follow-up, the Mood Spectrum Self-Report Measure – Lifetime Version assessed lifetime predisposition to subthreshold-syndromal mania/hypomania, depression, and sleep-circadian disturbances (insomnia, sleepiness, reduced sleep need, rhythm disruption). Mixture models derived profiles from baseline reward, impulsivity, and sleep-circadian variables. ResultsThree profiles were identified: 1) healthy (no reward or sleep-circadian disruption; n = 162); 2) moderate-risk (moderate reward and sleep-circadian disruption; n = 109); and 3) high-risk (high impulsivity and sleep-circadian disruption; n = 53). At baseline, the high-risk group had significantly higher mania/hypomania scores than the other groups but did not differ from the moderate-risk group in depression scores. Over the follow-up period, the high-risk and moderate-risk groups exhibited elevated mania/hypomania scores, whereas depression scores increased at a faster rate in the healthy group than in the other groups. ConclusionsCross-sectional and next-year predisposition to mania/hypomania is associated with a combination of heightened reward sensitivity and impulsivity, related reward circuitry activity, and sleep-circadian disturbances. These measures can be used to detect mania/hypomania risk and provide targets to guide and monitor interventions.

A History of Low-Dose Ethanol Shifts the Role of Ventral Hippocampus during Reward Seeking in Male Mice.

Although casual drinkers are a majority of the alcohol drinking population, understanding of the long-term effects of chronic exposure to lower levels of alcohol is limited. Chronic exposure to lower doses of ethanol may facilitate the development of alcohol use disorders, potentially because of ethanol effects on reward learning and motivation. Indeed, our previously published findings showed that chronic low-dose ethanol exposure enhanced motivation for sucrose in male, but not female, mice. As the ventral hippocampus (vHPC) is sensitive to disruption by higher doses of chronic ethanol and tracks reward-related information, we hypothesized that this region is impacted by low-dose ethanol and, further, that manipulating vHPC activity would alter reward motivation. In vivo electrophysiological recordings of vHPC population neural activity during progressive ratio testing revealed that vHPC activity was suppressed in the period immediately after reward seeking (lever press) in ethanol-naive controls, whereas suppression of vHPC activity anticipated reward seeking in ethanol-exposed mice. In both ethanol-naive and exposed mice, vHPC activity was suppressed before a reward magazine entry. Temporally selective inhibition of vHPC using optogenetics increased motivation for sucrose in ethanol-naive controls, but not in ethanol-exposed mice. Further, regardless of exposure history, vHPC inhibition promoted checking of the reward magazine, indicating a role for vHPC in reward tracking. There was no effect of chemogenetic inhibition of the vHPC either during training or testing on sucrose reward motivation. These results reveal novel ethanol-induced alterations in vHPC neural activity that shift how vHPC activity is able to regulate reward seeking.

Obese-associated gut microbes and derived phenolic metabolite as mediators of excessive motivation for food reward

BackgroundExcessive hedonic consumption is one of the main drivers for weight gain. Identifying contributors of this dysregulation would help to tackle obesity. The gut microbiome is altered during obesity and regulates host metabolism including food intake.ResultsBy using fecal material transplantation (FMT) from lean or obese mice into recipient mice, we demonstrated that gut microbes play a role in the regulation of food reward (i.e., wanting and learning processes associated with hedonic food intake) and could be responsible for excessive motivation to obtain sucrose pellets and alterations in dopaminergic and opioid markers in reward-related brain areas. Through untargeted metabolomic approach, we identified the 3-(3’-hydroxyphenyl)propanoic acid (33HPP) as highly positively correlated with the motivation. By administrating 33HPP in mice, we revealed its effects on food reward.ConclusionsOur data suggest that targeting the gut microbiota and its metabolites would be an interesting therapeutic strategy for compulsive eating, preventing inappropriate hedonic food intake.2kcCfMAdoVFagJjUNYJvh6Video

Reward, motivation and brain imaging in human healthy participants - A narrative review.

Over the past 20 years there has been an increasing number of brain imaging studies on the mechanisms underlying reward motivation in humans. This narrative review describes studies on the neural mechanisms associated with reward motivation and their relationships with cognitive function in healthy human participants. The brain's meso-limbic dopamine reward circuitry in humans is known to control reward-motivated behavior in humans. The medial and lateral Pre-Frontal Cortex (PFC) integrate motivation and cognitive control during decision-making and the dorsolateral PFC (dlPFC) integrates and transmits signals of reward to the mesolimbic and meso-cortical dopamine circuits and initiates motivated behavior. The thalamus and insula influence incentive processing in humans and the motor system plays a role in response to action control. There are reciprocal relationships between reward motivation, learning, memory, imagery, working memory, and attention. The most common method of assessing reward motivation is the monetary incentive delay task (DMRT) and there are several meta-analyses of this paradigm. Genetics modulates motivation reward, and dopamine provides the basis for the interaction between motivational and cognitive control. There is some evidence that male adolescents take more risky decisions than female adolescents and that the lateralization of reward-related DA release in the ventral striatum is confined to men. These studies have implications for our understanding of natural reward and psychiatric conditions like addiction, depression and ADHD. Furthermore, the association between reward and memory can help develop treatment techniques for drug addiction that interfere with consolidation of memory. Finally, there is a lack of research on reward motivation, genetics and sex differences and this can improve our understanding of the relationships between reward, motivation and the brain.

Israeli Arab Independent Health Clinics: Personal Incentive Systems and Motivational Rewards

The Israeli healthcare system is a universal system, based on the National Health Insurance Law 1995 (NHIL), which mandates all residents in the country to join one of four official health insurance organizations, known as ‘Kupat Holim’ (HMOs). This resulted in an increase in the accessibility of health services and their distribution throughout the country. Lack of physicians, especially in the peripheries, and the competition to recruit clients forced HMOs to change and expand the concept of operating medical services. One way was to establish independent health clinics (IHCs). The current study focuses on a social and cultural phenomenon that was changed and expanded following the NHIL. The research literature lacks studies addressing IHCs in the context of the impact of the NHIL on Arab society. The research design is mixed methods with a qualitative stage followed by a quantitative stage. Specifically compiled research interviews and questionnaires were built to collect information. The main findings of the studies indicated that most physicians and managers recognized the NHIL and its contribution to the population. Addressing social and environmental rewards and deciding on moral rewards at an early stage anchored in the contract from the beginning was significant and strengthened the future of contracts between HMOs and self-employed physicians. Findings and conclusions of the study indicated a need to continue operating IHCs on condition they kept initial promises and provided feedback to physicians from time to time while improving terms of engagement, visits, and problem solving when needed in a timely manner.

Effects of an experimentally induced inflammatory stimulus on motivational behavior in remitted depressed patients

BackgroundAcute inflammation is associated with sickness behavior characterized by reduced motivation for pleasurable activities in humans. The current study investigated the effect of an experimentally induced inflammatory stimulus on motivational reward in people who remitted from depression. MethodsThis randomized, double-blind crossover study involved 12 participants, 5 with remitted major depressive disorder (rMDD) and 7 healthy controls (HC), who received an injection of typhoid vaccine and placebo (or vice-versa) intramuscularly at least one week apart. At baseline and between 4 and 6 h post-injection on both days, participant mood was measured using the profile of mood states (POMS), and injection blood samples were collected for cytokines measurement. All participants completed the Effort Expenditure for Rewards Task (EEfRT), a behavioral paradigm measuring effort-based decision-making before and 4 h post-both injections. Generalized linear mixed modeling was used to evaluate group differences in choosing the hard over easy task to obtain a monetary reward. ResultsTyphoid vaccine increased IL-6 in all participants. On the EEfRT, a significant interaction between treatment condition (typhoid vs. placebo) and participant group (HC vs. rMDD) was found (p = .004). Analyses of simple effects within treatment conditions found that after placebo, HCs were more likely to choose the harder task than rMDD (OR = 3.21; p = .013). However, after the typhoid vaccine, no differences were found between rMDD and HC (p = .397). Analyses within participant groups found that the probability of choosing a hard task was higher after placebo for HC (OR = 1.37; p = .045), but not different within rMDD (p = .241). For HC at baseline, mood was significantly lower following injection with typhoid vaccine, relative to placebo (b = −1.03, p < .001); however, this effect should be considered coincidental, given that mood rating was taken prior to injection. For rMDD patients 4–6 h post-injection, mood was significantly lower following typhoid vaccine, relative to placebo (b = −0.981, p < .001 b = −0.77, p < .001). Finally, for HC receiving placebo, mood was significantly lower 4–6 h post-injection, relative to baseline (b = −1.76, p < .001). ConclusionsOur preliminary findings suggest persistent deficits in motivational reward processing function despite clinical improvement in remitted depressed patients.

Amygdala and nucleus accumbens activation during reward anticipation moderates the association between life stressor frequency and depressive symptoms

BackgroundLife stressors confer risk for depressive symptoms, but individuals vary in the extent of their sensitivity to life stressors. One protective factor may be an individual's level of reward sensitivity, e.g., a stronger neurobiological response to environmental rewards may mitigate emotional responses to stressors. However, the nature of neurobiological reward sensitivity that corresponds with stress resilience is unknown. Further, this model is untested in adolescence, when life stressor frequency and depression increase. MethodsWe tested the hypothesis that stronger reward-related activation in the left and right nucleus accumbens (NAc), amygdala, and medial prefrontal cortex (mPFC) attenuates the strength of the stress-depression relation. We measured BOLD activation throughout Win and Lose blocks of a monetary reward task, as well as during anticipation and outcome phases of the task. Participants (N = 151, ages 13–19) were recruited to be stratified on risk for mood disorders to enhance variance in depressive symptoms. ResultsActivation during anticipation of rewards in the bilateral amygdala and NAc, but not mPFC, buffered the association between life stressors and depressive symptoms. This buffering effect was not found for reward outcome activation or activation across Win blocks. ConclusionsResults highlight the importance of reward anticipation activation of subcortical structures in attenuating the stress-depression link, suggesting that reward motivation may be a cognitive mechanism through which this stress buffering occurs.

Ghrelin at the interface of hunger, reward and obesity

AbstractGhrelin, a stomach-derived hunger and appetite signal, drives behaviors that ensure we seek out and consume foods, not only in situations of energy deficit but also when anticipating palatable foods. Key target pathways for ghrelin include the orexigenic agouti-related peptide (AgRP) neurones in the hypothalamic arcuate nucleus (Arc), that appear to confer the unpleasant feelings of hunger. They also include dopamine neurones in the ventral tegmental area, where ghrelin heightens motivation for food rewards. Recently, we have employed a variety of neural circuit mapping techniques in rodents to help clarify the function of populations of ghrelin-responsive targets. We found that 1) chemogenetic activation of ghrelin-responsive cells in the Arc is sufficient to drive a feeding response and to induce food-motivated behaviour and 2) that dopamine neurones in the VTA are activated when mice are exposed to cues that predict a food reward than to its retrieval, as revealed by fiber photometry recordings from these cells. Further studies aim to determine the role of ghrelin-responsive cells in the parabrachial nucleus of the brainstem. Overall, the brain ghrelin signalling system is well positioned to integrate the response to hunger, enhanced by both intrinsic and external cues and in ways that are relevant to curb over-eating in obesity.Disclosure of InterestNone Declared

A guide to the AfterDeath: Maimonides on olam ha-ba’

AbstractThis article analyses Moses Maimonides' account of the AfterDeath and, more specifically, of olam ha-ba’ (lit.: the world to come), the state of ultimate human happiness and perfection (in contrast to this world). Maimonides is unequivocal about what olam ha-ba’ is not. Contrary to a competing medieval Jewish tradition, it is utterly incorporeal and, contrary to rabbinic tradition, it is not a motivational reward nor compensation for undeserved suffering in a theodicy. Instead, Maimonides gives two positive accounts of the metaphysics of olam ha-ba’. The first is an intellectualist account on which the denizens of olam ha-ba’ are perfected intellects engaged in intellectual apprehension of the deity. The second is sceptical: it denies that humans have any understanding or knowledge (‘ilm, episteme) of olam ha-ba’ and claims that all language used to describe it is purely equivocal or homonymous, although it allows that some immutable thing, whatever it is, survives death. Instead of being a motivational reward or compensation, olam ha-ba’ is the end, that is, final cause or telos, of the best possible human life in this world at which one aims and which one attempts to approximate even if one cannot actually realize it.

NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses.

Chronic stress can produce reward system deficits (i.e., anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here that the neuronal activity-regulated transcription factor, NPAS4, in the mPFC is regulated by chronic social defeat stress (CSDS), and it is required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation in the mice. Interestingly, NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior. We also find that mPFC NPAS4 is required for CSDS-induced reductions in pyramidal neuron dendritic spine density, excitatory synaptic transmission, and presynaptic function, revealing a relationship between perturbation in excitatory synaptic transmission and the expression of anhedonia-like behavior in the mice. Finally, analysis of the mice mPFC tissues revealed that NPAS4 regulates the expression of numerous genes linked to glutamatergic synapses and ribosomal function, the expression of upregulated genes in CSDS-susceptible animals, and differentially expressed genes in postmortem human brains of patients with common neuropsychiatric disorders, including depression. Together, our findings position NPAS4 as a key mediator of chronic stress-induced hypofrontal states and anhedonia-like behavior.

Supplemental Material for Reward Motivation More Consistently Modulates Memory for Younger Compared to Older Adults in a Directed Forgetting Task

Supplemental Material for Reward Motivation More Consistently Modulates Memory for Younger Compared to Older Adults in a Directed Forgetting Task

Reduced sensitivity but intact motivation to monetary rewards and reversal learning in obesity

BackgroundObesity has been linked to altered reward processing but little is known about which components of reward processing including motivation, sensitivity and learning are impaired in obesity. We examined whether obesity compared to healthy weight controls is associated with differences in distinct subdomains of reward processing. To this end, we used two established paradigms, namely the Effort Expenditure for Rewards task (EEfRT) and the Probabilistic Reversal Learning Task (PRLT). Methods30 individuals with obesity (OBS) and 30 healthy weight control subjects (HC) were included in the study. Generalized estimating equation models were used to analyze EEfRT choice behavior. PRLT data was analyzed using both conventional behavioral variables of choices and computational models. ResultsOur findings from the different tasks speak in favor of a hyposensitivity to non-food rewards in obesity. OBS did not make fewer overall hard task selections compared to HC in the EEfRT suggesting generally intact non-food reward motivation. However, in highly rewarding trials (i.e.,trials with high reward magnitude and high reward probability),OBSmadefewer hard task selections compared to normal weight subjects suggesting decreased sensitivity to highly rewarding non-food reinforcers. Hyposensitivity to non-food rewards was also evident in OBS in the PRLT as evidenced by lower win-stay probability compared to HC. Our computational modelling analyses revealed decreased stochasticity but intact reward and punishment learning rates in OBS. ConclusionsOur findings provide evidence for intact reward motivation and learning in OBS but lower reward sensitivity which is linked to stochasticity of choices in a non-food context. These findings might provide further insight into the mechanism underlying dysfunctional choices in obesity.

Male DAT Val559 Mice Exhibit Compulsive Behavior under Devalued Reward Conditions Accompanied by Cellular and Pharmacological Changes.

Identified across multiple psychiatric disorders, the dopamine (DA) transporter (DAT) Ala559Val substitution triggers non-vesicular, anomalous DA efflux (ADE), perturbing DA neurotransmission and behavior. We have shown that DAT Val559 mice display a waiting impulsivity and changes in cognitive performance associated with enhanced reward motivation. Here, utilizing a within-subject, lever-pressing paradigm designed to bias the formation of goal-directed or habitual behavior, we demonstrate that DAT Val559 mice modulate their nose poke behavior appropriately to match context, but demonstrate a perseverative checking behavior. Although DAT Val559 mice display no issues with the cognitive flexibility required to acquire and re-learn a visual pairwise discrimination task, devaluation of reward evoked habitual reward seeking in DAT Val559 mutants in operant tasks regardless of reinforcement schedule. The direct DA agonist apomorphine also elicits locomotor stereotypies in DAT Val559, but not WT mice. Our observation that dendritic spine density is increased in the dorsal medial striatum (DMS) of DAT Val559 mice speaks to an imbalance in striatal circuitry that might underlie the propensity of DAT Val559 mutants to exhibit compulsive behaviors when reward is devalued. Thus, DAT Val559 mice represent a model for dissection of how altered DA signaling perturbs circuits that normally balance habitual and goal-directed behaviors.