Reward Motivation Research Articles

Developmental trajectory of social reward motivation from early adolescence into adulthood in female and male Long-Evans rats.

Most studies of adolescent and adult behavior involved one age group of each, whereas the dynamic changes in brain development suggest that there may be behavioral flux in adolescence. In two studies, we investigated developmental changes in social reward motivation in female and male Long-Evans rats from prepuberty to early adulthood in a social operant conditioning task. Given the earlier onset of puberty in females than in males, we predicted the course of social reward development would differ between the sexes. Overall, the pattern of results from both studies suggests that the trajectory of social motivation across adolescence is characterized by upward and downward shifts that do not depend on the sex of the rats. During training, in both studies, the mean number of social gate openings and percentage of social gate openings was higher at P30 (prepubertal, early adolescence) and P50 (late adolescence) than at P40 (mid adolescence) and P70 (adulthood) irrespective of sex. Nevertheless, the specific age comparisons that were significant depended on the study. In both studies, P30 rats had greater levels of social motivation than did adults in accessing a social reward when increased effort was required (progressive ratio tests). In an extinction test, only P30 and P50 rats continued to show more nose-pokes at the previously social gate than at the nonsocial gate, suggesting resistance to extinction. The results highlight the importance of characterizing behavior at several timepoints in adolescence to understand the neural mechanisms, many of which show similar discontinuities as they develop across adolescence.

Brain stimulation over the left DLPFC enhances motivation for effortful rewards in patients with major depressive disorder

BackgroundAmotivation is a typical feature in major depressive disorder (MDD), which produces reduced willingness to exert effort. The dorsolateral prefrontal cortex (DLPFC) is a crucial structure in goal-directed actions and therefore is a potential target in modulating effortful motivation. However, it remains unclear whether the intervention is effective for patients with MDD. MethodsWe employed transcranial magnetic stimulation (TMS), computational modelling and event-related potentials (ERPs) to reveal the causal relationship between the left DLPFC and motivation for effortful rewards in MDD. Fifty patients underwent both active and sham TMS sessions, each followed by performing an Effort-Expenditure for Rewards Task, during which participants chose and implemented between low-effort/low-reward and high-effort/high-reward options. ResultsThe patients showed increased willingness to exert effort for rewards during the DLPFC facilitated session, compared with the sham session. They also had a trend in larger P3 amplitude for motivated attention toward chosen options, larger CNV during preparing for effort exertion, and larger SPN during anticipating a high reward. Besides, while behavior indexes for effortful choices were negatively related to depression severity in the sham session, this correlation was weakened in the active stimulation session. ConclusionsThese findings provide behavioral, computational, and neural evidence for the left DLPFC on effortful motivation for rewards. Facilitated DLPFC improves motor preparation and value anticipation after making decisions especially for highly effortful rewards in MDD. Facilitated DLPFC also has a potential function in enhancing motivated attention during cost-benefit trade-off. This neuromodulation effect provides a potential treatment for improving motivation in clinics.

Neural Hyperresponsivity During the Anticipation of Tangible Social and Nonsocial Rewards in Autism Spectrum Disorder: A Concurrent Neuroimaging and Facial Electromyography Study

BackgroundAtypical anticipation of social reward has been shown to lie at the core of the social challenges faced by individuals with autism spectrum disorder (ASD). However, previous research has yielded inconsistent results and has often overlooked crucial characteristics of stimuli. Here, we investigated ASD reward processing using social and nonsocial tangible stimuli, carefully matched on several key dimensions. MethodsWe examined the anticipation and consumption of social (interpersonal touch) and nonsocial (flavored milk) rewards in 25 high-functioning individuals with ASD and 25 neurotypical adult individuals. In addition to subjective ratings of wanting and liking, we measured physical energetic expenditure to obtain the rewards, brain activity with neuroimaging, and facial reactions through electromyography on a trial-by-trial basis. ResultsParticipants with ASD did not exhibit reduced motivation for social or nonsocial rewards; their subjective ratings, motivated efforts, and facial reactions were comparable to those of neurotypical participants. However, anticipation of higher-value rewards increased neural activation in lateral parietal cortices, sensorimotor regions, and the orbitofrontal cortex. Moreover, participants with ASD exhibited hyperconnectivity between frontal medial regions and occipital regions and the thalamus. ConclusionsIndividuals with ASD who experienced rewards with tangible characteristics, whether social or nonsocial, displayed typical subjective and objective motivational and hedonic responses. Notably, the observed hyperactivations in sensory and attentional nodes during anticipation suggest atypical sensory overprocessing of forthcoming rewards rather than decreased reward value. While these atypicalities may not have manifested in observable behavior here, they could impact real-life social interactions that require nuanced predictions, potentially leading to the misperception of reduced interest in rewarding social stimuli in ASD.

Effort-cost decision-making associated with negative symptoms in schizophrenia and bipolar disorder

Motivational deficits and reduced goal-directed behavior for external rewards have long been considered an important features of negative symptoms in patients with schizophrenia (SCZ). Negative symptoms have also a high prevalence in bipolar disorder (BP). We used a transdiagnostic approach in order to examine association between negative symptoms and effort allocation for monetary rewards. 41 patients with SCZ and 34 patients with BP were enrolled in the study along with 41 healthy controls (HC). Effort-Expenditure for Rewards Task (EEfRT) was used to measure subjects' effort allocation for monetary rewards. Generalized estimating equation models were used to analyze EEfRT choice behavior. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). SCZ and BP groups expended lower effort to obtain a monetary rewards compared to HC. Severity of negative symptoms was negatively correlated with EEfRT performance in both diagnostic groups. Each diagnostic group showed lower effort allocation for monetary rewards compared to HC suggesting reduced motivation for monetary rewards. In addition, our results suggest that abnormal effort-based decision-making might be a transdiagnostic factor underlying negative symptoms.

Characterisation of behaviours relevant to apathy syndrome in the aged male rat

Apathy is a complex psychiatric syndrome characterised by motivational deficit, emotional blunting and cognitive changes. It occurs alongside a broad range of neurological disorders, but also occurs in otherwise healthy ageing. Despite its clinical prevalence, apathy does not yet have a designated treatment strategy. Generation of a translational animal model of apathy syndrome would facilitate the development of novel treatments. Given the multidimensional nature of apathy, a model cannot be achieved with a single behavioural test. Using a battery of behavioural tests we investigated whether aged rats exhibit behavioural deficits across different domains relevant to apathy. Using the effort for reward and progressive ratio tasks we found that aged male rats (21–27 months) show intact reward motivation. Using the novelty supressed feeding test and position-based object exploration we found aged rats showed increased anxiety-like behaviour inconsistent with emotional blunting. The sucrose preference test and reward learning assay showed intact reward sensitivity and reward-related cognition in aged rats. However, using a bowl-digging version of the probabilistic reversal learning task, we found a deficit in cognitive flexibility in aged rats that did not translate across to a touchscreen version of the task. While these data reveal important changes in cognitive flexibility and anxiety associated with ageing, aged rats do not show deficits across other behavioural domains relevant to apathy. This suggests that aged rats are not a suitable model for age-related apathy syndrome. These findings contrast with previous work in mice, revealing important species differences in behaviours relevant to apathy syndrome in ageing.

Potential-Based Reward Shaping for Intrinsic Motivation (Student Abstract)

Recently there has been a proliferation of intrinsic motivation (IM) reward shaping methods to learn in complex and sparse-reward environments. These methods can often inadvertently change the set of optimal policies in an environment, leading to suboptimal behavior. Previous work on mitigating the risks of reward shaping, particularly through potential-based reward shaping (PBRS), has not been applicable to many IM methods, as they are often complex, trainable functions themselves, and therefore dependent on a wider set of variables than the traditional reward functions that PBRS was developed for. We present an extension to PBRS that we show preserves the set of optimal policies under a more general set of functions than has been previously demonstrated. We also present Potential-Based Intrinsic Motivation (PBIM), a method for converting IM rewards into a potential-based form that are useable without altering the set of optimal policies. Testing in the MiniGrid DoorKey environment, we demonstrate that PBIM successfully prevents the agent from converging to a suboptimal policy and can speed up training.

Sex and pubertal variation in reward-related behavior and neural activation in early adolescents

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9–13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Activation patterns in male and female forebrain circuitries during food consumption under novelty.

The influence of novelty on feeding behavior is significant and can override both homeostatic and hedonic drives due to the uncertainty of potential danger. Previous work found that novel food hypophagia is enhanced in a novel environment and that males habituate faster than females. The current study's aim was to identify the neural substrates of separate effects of food and context novelty. Adult male and female rats were tested for consumption of a novel or familiar food in either a familiar or in a novel context. Test-induced Fos expression was measured in the amygdalar, thalamic, striatal, and prefrontal cortex regions that are important for appetitive responding, contextual processing, and reward motivation. Food and context novelty induced strikingly different activation patterns. Novel context induced Fos robustly in almost every region analyzed, including the central (CEA) and basolateral complex nuclei of the amygdala, the thalamic paraventricular (PVT) and reuniens nuclei, the nucleus accumbens (ACB), the medial prefrontal cortex prelimbic and infralimbic areas, and the dorsal agranular insular cortex (AI). Novel food induced Fos in a few select regions: the CEA, anterior basomedial nucleus of the amygdala, anterior PVT, and posterior AI. There were also sex differences in activation patterns. The capsular and lateral CEA had greater activation for male groups and the anterior PVT, ACB ventral core and shell had greater activation for female groups. These activation patterns and correlations between regions, suggest that distinct functional circuitries control feeding behavior when food is novel and when eating occurs in a novel environment.

A neuronal coping mechanism linking stress-induced anxiety to motivation for reward.

Stress coping involves innate and active motivational behaviors that reduce anxiety under stressful situations. However, the neuronal bases directly linking stress, anxiety, and motivation are largely unknown. Here, we show that acute stressors activate mouse GABAergic neurons in the interpeduncular nucleus (IPN). Stress-coping behavior including self-grooming and reward behavior including sucrose consumption inherently reduced IPN GABAergic neuron activity. Optogenetic silencing of IPN GABAergic neuron activation during acute stress episodes mimicked coping strategies and alleviated anxiety-like behavior. In a mouse model of stress-enhanced motivation for sucrose seeking, photoinhibition of IPN GABAergic neurons reduced stress-induced motivation for sucrose, whereas photoactivation of IPN GABAergic neurons or excitatory inputs from medial habenula potentiated sucrose seeking. Single-cell sequencing, fiber photometry, and optogenetic experiments revealed that stress-activated IPN GABAergic neurons that drive motivated sucrose seeking express somatostatin. Together, these data suggest that stress induces innate behaviors and motivates reward seeking to oppose IPN neuronal activation as an anxiolytic stress-coping mechanism.

Predictors of clinically significant anhedonia in refractory epilepsy

Background: Anhedonia, the inability to feel pleasure or motivation for reward, is a core feature of depression in epilepsy, but can occur independent from depression. It is reported in over a third of people with epilepsy and has a significant impact on quality of life. Objectives: This study determined whether specific features of medication refractory epilepsy are predictive of anhedonia. Design: We assessed 267 patients with medication refractory epilepsy for anhedonia, primarily using the clinically validated Snaith-Hamilton Pleasure Scale (SHAPS) scale. Methods: Patients with clinically significant anhedonia were compared with those without for key demographics, epilepsy characteristics and medication using a logistic regression analysis. Results: We found that seizure frequency (p < 0.01) but not duration of epilepsy was significantly associated with anhedonia. We also found that benzodiazepine use was significantly associated (p = 0.01) with anhedonia, and levetiracetam/brivaracetam and sodium valproate were significantly negatively associated with anhedonia (0.01 and 0.03 respectively). Conclusion: High seizure burden in medication refractory epilepsy is significantly associated with anhedonia. Specific antiseizure medications are also associated with the development of anhedonia, but it is unclear whether their use is causative or influenced by the presence of anhedonia.

Orbitofrontal intronic circular RNA from Nrxn3 mediates reward learning and motivation for reward

The orbitofrontal cortex (OFC) is a vital component of brain reward circuitry that is important for reward seeking behavior. However, OFC-mediated molecular mechanisms underlying rewarding behavior are understudied. Here, we report the first circular RNA (circRNA) profile associated with appetitive reward and identify regulation of 92 OFC circRNAs by sucrose self-administration. Among these changes, we observed downregulation of circNrxn3, a circRNA originating from neurexin 3 (Nrxn3), a gene involved in synaptogenesis, learning, and memory. Transcriptomic profiling via RNA sequencing and qPCR of the OFC following in vivo knock-down of circNrxn3 revealed differential regulation of genes associated with pathways important for learning and memory and altered splicing of Nrxn3. Furthermore, circNrxn3 knock-down enhanced sucrose self-administration and motivation for sucrose. Using RNA-immunoprecipitation, we report binding of circNrxn3 to the known Nrxn3 splicing factor SAM68. circNrxn3 is the first reported circRNA capable of regulating reward behavior and circNrxn3-mediated interactions with SAM68 may impact subsequent downstream processing of RNAs such as the regulation of gene expression and splicing.

Habit-, reward- and fear-related motivations in alcohol use disorder: A one-year prospective study

ObjectiveCross-sectional studies show that habitual use of alcohol is associated with severity of alcohol dependence reflected across a range of domains and lower number of detoxifications in multiple settings. In this study, we investigated whether alcohol use disorder (AUD) patients with greater habitual use of alcohol at baseline showed worse outcomes after one year of follow-up. MethodsA sample of inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorder (AUD) was assessed at baseline (n = 50) and after one year (n = 30). The Habit, Reward, and Fear Scale (HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) drives for alcohol use, the Alcohol Dependence Scale (ADS) was used to assess clinical outcomes, and the Depression, Anxiety and Stress Scale (DASS-21) was used to quantify and control for associated affective symptoms. ResultsThere was a significant reduction in the three HRFS scores at the follow-up. Regression analyses demonstrated that greater habit- and fear-related drives at baseline predicted greater decreases in the ADS scores at the endpoint. However, after controlling for age, sex and affective symptoms, only reward and fear were associated with reductions in ADS scores at the end of one year. Prescriptions of naltrexone and antidepressants/benzodiazepines did not predict decreases in reward and fear-related motivations. ConclusionAlthough we were unable to confirm that habitual subscores at baseline predict worse long-term outcomes among inpatients with AUD, we found that a greater fear and reward motives for the use of alcohol predicted a greater magnitude of improvement in the AUD symptoms after one year. We hope that these findings will help develop new approaches toward AUD treatment and inform models of addiction research.

Activation of the basolateral or the central amygdala dampened the incentive motivation for food reward on high fixed-ratio schedules

The amygdala plays crucial roles in emotional processing, motivated behaviors, and stress responses. It receives sensory information and modulates fear- and anxiety-related behaviors. Neuronal activations are induced in the basolateral complex of the amygdala (BLA) and the central nucleus of the amygdala (CeA) when exposing to acute stress, leading to increased alertness and proper behavioral adaptation. Previous studies have shown that animals displayed a decrease in appetitive motivated behaviors under stress conditions. However, whether the hyperactive amygdala is responsible for the decrease in appetitive motivated behaviors remains unknown. In this study, we aimed to examine the role of BLA or CeA activation in effort-based motivated behavior. We pharmacologically activated the BLA or the CeA with N-methyl-D-aspartate (NMDA) before the lever-pressing for food reward test on different fixed-ratio (FR) schedules (FR1, FR16, or FR32) in male Long-Evans rats. Our data showed that activation of either the BLA or the CeA with NMDA (0.05 μg in 0.5 μl per site) decreased the lever-pressing behavior on higher FR schedules of FR16 and FR32, but not on the FR1 test. Importantly, locomotor activity and free-feeding food intake were intact under amygdala activation, suggesting that the decrease in lever-pressing behavior was not due to motor disablement or decreased appetite. These results suggested that activation of the BLA or the CeA negatively impaired the effort-based motivated behavior that the animals were less willing to work for food reward.

Chronic jet lag reduces motivation and affects other mood-related behaviors in male mice.

Introduction: The circadian system regulates various physiological processes such as sleep-wake cycles, hormone secretion, metabolism, and the reaction to both natural and drug-based rewards. Chronic disruption of the circadian system caused by unsteady synchronization with light-dark (LD) schedules, such as advancing chronic jet lag (CJL), leads to adverse physiological effects and pathologies, and is linked with changes in mood and depressive behaviors in humans and rodent models. Methods: C57BL/6J male mice were subjected to circadian disruption through phase advances of 6h every 2days (CJL +6/2). Mice under 12:12-h LD cycle were used as controls. After 8weeks under these conditions, a battery of behavioral tests was performed to assess if mood-related behaviors were affected. Results: Compared to controls under 24h LD cycles, mice under CJL presented desynchronization of activity-rest rhythms that led to several behavioral impairments, including a decrease in motivation for food reward, and an increase in anxiety, anhedonia, and depressive-like behavior. Conclusion: Chronic circadian disruption, caused by an experimental CJL protocol, affects mood-related and reward-related behaviors in mice. Understanding the importance of the circadian system and its potential role for disruption due to CJL is important for maintaining good health and well-being.

The Role of Genetically Distinct Central Amygdala Neurons in Appetitive and Aversive Responding Assayed with a Novel Dual Valence Operant Conditioning Paradigm.

To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Jikomes et al., 2016; Heinz et al., 2017), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nose poke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock). This design allows for both within-subject and between-subject comparisons as animals respond to appetitive and aversive cues. The central nucleus of the amygdala (CeA) is implicated in the regulation of responses to stimuli of either valence. Considering its role in threat processing (Wilensky et al., 2006; Haubensak et al., 2010) and regulation of incentive salience (Warlow and Berridge, 2021), it is important to examine the contribution of the CeA to mechanisms potentially underlying comorbid dysregulation of avoidance and reward (Sinha, 2008; Bolton et al., 2009). Using this paradigm, we tested the role of two molecularly defined CeA subtypes previously linked to consummatory and defensive behaviors. Significant strain differences in the acquisition and performance of the task were observed. Bidirectional chemogenetic manipulation of CeA somatostatin (SOM) neurons altered motivation for reward and perseveration of reward-seeking responses on avoidance trials. Manipulation of corticotropin-releasing factor neurons (CRF) had no significant effect on food reward consumption, motivation, or task performance. This paradigm will facilitate investigations into the neuronal mechanisms controlling motivated behavior across valences.

Bile acids modulate reinstatement of cocaine conditioned place preference and accumbal dopamine dynamics without compromising appetitive learning

Psychostimulants target the dopamine transporter (DAT) to elicit their psychomotor actions. Bile acids (BAs) can also bind to DAT and reduce behavioral responses to cocaine, suggesting a potential therapeutic application of BAs in psychostimulant use disorder. Here, we investigate the potential of BAs to decrease drug-primed reinstatement when administered during an abstinence phase. To do this, after successful development of cocaine-associated contextual place preference (cocaine CPP), cocaine administration was terminated, and animals treated with vehicle or obeticholic acid (OCA). When preference for the cocaine-associated context was extinguished, mice were challenged with a single priming dose of cocaine, and reinstatement of cocaine-associated contextual preference was measured. Animals treated with OCA demonstrate a significantly lower reinstatement for cocaine CPP. OCA also impairs the ability of cocaine to reduce the clearance rate of electrically stimulated dopamine release and diminishes the area under the curve (AUC) observed with amperometry. Furthermore, the AUC of the amperometric signal positively correlates with the reinstatement index. Using operant feeding devices, we demonstrate that OCA has no effect on contextual learning or motivation for natural rewards. These data highlight OCA as a potential therapeutic for cocaine use disorder.

Reward motivation more consistently modulates memory for younger compared to older adults in a directed forgetting task.

Remembering and forgetting are both important processes of a healthy memory system, but both processes can show age-related decline. Reward anticipation is effective at improving remembering in both younger and older adults, but little is known about the effects of incentives on forgetting. In four online experiments, we examined whether reward motivation modulates intentional remembering and forgetting in younger and older adults, and systematically varied the presentation of reward cues during encoding to test whether the temporal dynamics of reward anticipation are important for directed forgetting performance. Both age groups showed directed forgetting effects such that participants remembered more items they were instructed to remember than instructed to forget, but across experiments, we found no evidence that reward incentives improved forgetting in either age group. Younger adults consistently exhibited reward-modulated memory across experiments and varying the timing of the reward cue had little impact on performance. Older adults displayed inconsistent effects of reward on memory, only when reward anticipation was elicited closer to the middle of the experimental trial did it enhance memory in this task. Overall, the findings from the current set of experiments indicate that reward anticipation improved memory, but not forgetting, and most consistently for younger adults, compared to older adults. Further, older adults' cognitive performance may be more sensitive to the placement and timing of reward anticipation in the experimental trial perhaps due to the time course of reward anticipation and interactions with the hippocampus that may show age-related change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Strain-specific changes in nucleus accumbens transcriptome and motivation for palatable food reward in mice exposed to maternal separation.

In humans, adversity in childhood exerts enduring effects on brain and increases the vulnerability to psychiatric diseases. It also leads to a higher risk of eating disorders and obesity. Maternal separation (MS) in mice has been used as a proxy of stress during infancy. We hypothesized that MS in mice affects motivation to obtain palatable food in adulthood and changes gene expression in reward system. Male and female pups from C57Bl/6J and C3H/HeN mice strains were subjected to a daily MS protocol from postnatal day (PND) 2 to PND14. At adulthood, their motivation for palatable food reward was assessed in operant cages. Compared to control mice, male and female C3H/HeN mice exposed to MS increased their instrumental response for palatable food, especially when the effort required to obtain the reward was high. Importantly, this effect is shown in animals fed ad libitum. Transcriptional analysis revealed 375 genes differentially expressed in the nucleus accumbens of male MS C3H/HeN mice compared to the control group, some of these being associated with the regulation of the reward system (e.g., Gnas, Pnoc). Interestingly, C57Bl/6J mice exposed to MS did not show alterations in their motivation to obtain a palatable reward, nor significant changes in gene expression in the nucleus accumbens. MS produces long-lasting changes in motivation for palatable food in C3H/HeN mice, but has no impact in C57Bl/6J mice. These behavioral alterations are accompanied by drastic changes in gene expression in the nucleus accumbens, a key structure in the regulation of motivational processes.

Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice

RationaleMotivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task.ObjectivesHere, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans.MethodUsing male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment.ResultsAmphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance.ConclusionThese data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context.

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.