Reward Perception Research Articles

Functional near-infrared spectroscopy assessment of reward perception based on visual self-expression: Coloring, doodling, and free drawing

Visual self-expression helps with attention and improves health and well-being. Few studies have examined reward pathway activation during different visual art tasks. This pilot study is the first to examine brain activation via functional near-infrared spectroscopy (fNIRS) during three distinct drawing tasks—coloring, doodling, and free drawing. Participants (11 men, 15 women; 8 artists, 16 non-artists) engaged in each task separated by equal intervals of rest in a block design experimental protocol. Additional data included a pre- and post survey of self-perceptions of creativity, prior experience with drawing tasks, and reflections on study participation. Overall, the three visual arts tasks resulted in significant activation of the medial prefrontal cortex compared to the rest conditions. The doodling condition resulted in maximum activation of the medial prefrontal cortex compared to coloring and free drawing; however, differences between the drawing conditions were not statistically significant. Emergent differences were seen between artists and non-artists for coloring and doodling. All three visual self-expression tasks activated the medial prefrontal cortex, indicating potential clinical applications of reward perception through art making. Participants improved in their self-perceptions of problem solving and having good ideas. Participants found the drawing tasks relaxing but wanted more time per task. Further study with varied art media and longer time on tasks are needed to determine potential interactions between participants’ backgrounds and reward activation.

Immediate perception of a reward is distinct from the reward's long-term salience.

Reward perception guides all aspects of animal behavior. However, the relationship between the perceived value of a reward, the latent value of a reward, and the behavioral response remains unclear. Here we report that, given a choice between two sweet and chemically similar sugars-L- and D-arabinose-Drosophila melanogaster prefers D- over L- arabinose, but forms long-term memories of L-arabinose more reliably. Behavioral assays indicate that L-arabinose-generated memories require sugar receptor Gr43a, and calcium imaging and electrophysiological recordings indicate that L- and D-arabinose differentially activate Gr43a-expressing neurons. We posit that the immediate valence of a reward is not always predictive of the long-term reinforcement value of that reward, and that a subset of sugar-sensing neurons may generate distinct representations of similar sugars, allowing for rapid assessment of the salient features of various sugar rewards and generation of reward-specific behaviors. However, how sensory neurons communicate information about L-arabinose quality and concentration-features relevant for long-term memory-remains unknown.

Devaluation of Rewards for the Future Is Associated With Schizotypal Personality Features

ObjectiveEmpirical evidence has suggested that schizophrenia is associated with dysfunctions in the reward system and working memory. However, little is known about individuals at risk for schizophrenia. In particular, it is not known if those with schizotypal personality features will show similar deficits in these two domains. This study examined whether individuals with schizotypal personality disorder features will subjectively devalue potential rewards in the future and show changes in their decision‐making behaviour, compared with healthy controls, and whether this devaluation is inversely associated with working memory performance.MethodA total of 44 participants with schizotypal personality features and 22 healthy control participants without schizotypal personality features completed the Monetary‐Choice Questionnaire, the Cambridge Gambling Task, and number and letter span tasks, which assessed delay‐discounting rate, decision‐making behaviour, and working memory, respectively.ResultsThe results showed that participants with schizotypal personality features, especially those with negative features, valued delayed rewards in the future to a lesser extent than healthy control participants. However, there was no significant group difference in decision‐making on the Cambridge Gambling Task. Moreover, the delay‐discounting rate of individuals with schizotypal personality features correlated significantly with working memory performance.ConclusionThe findings suggest that people with schizotypal personality features may be impaired in future reward perception and that this impairment is related to their working memory ability, although their capacity to make decisions is not affected.

Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats

We explored the impact of exposure to an obesogenic diet (High Fat–High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed.

Cdk5 Modulates Long-Term Synaptic Plasticity and Motor Learning in Dorsolateral Striatum.

The striatum controls multiple cognitive aspects including motivation, reward perception, decision-making and motor planning. In particular, the dorsolateral striatum contributes to motor learning. Here we define an approach for investigating synaptic plasticity in mouse dorsolateral cortico-striatal circuitry and interrogate the relative contributions of neurotransmitter receptors and intracellular signaling components. Consistent with previous studies, we show that long-term potentiation (LTP) in cortico-striatal circuitry is facilitated by dopamine, and requires activation of D1-dopamine receptors, as well as NMDA receptors (NMDAR) and their calcium-dependent downstream effectors, including CaMKII. Moreover, we assessed the contribution of the protein kinase Cdk5, a key neuronal signaling molecule, in cortico-striatal LTP. Pharmacological Cdk5 inhibition, brain-wide Cdk5 conditional knockout, or viral-mediated dorsolateral striatal-specific loss of Cdk5 all impaired dopamine-facilitated LTP or D1-dopamine receptor-facilitated LTP. Selective loss of Cdk5 in dorsolateral striatum increased locomotor activity and attenuated motor learning. Taken together, we report an approach for studying synaptic plasticity in mouse dorsolateral striatum and critically implicate D1-dopamine receptor, NMDAR, Cdk5, and CaMKII in cortico-striatal plasticity. Furthermore, we associate striatal plasticity deficits with effects upon behaviors mediated by this circuitry. This approach should prove useful for the study of the molecular basis of plasticity in the dorsolateral striatum.

Caffeinated Forage Tricks Honeybees into Increasing Foraging and Recruitment Behaviors

In pollination, plants provide food reward to pollinators who in turn enhance plant reproduction by transferring pollen, making the relationship largely cooperative; however, because the interests of plants and pollinators do not always align, there exists the potential for conflict, where it may benefit both to cheat the other [1, 2]. Plants may even resort to chemistry: caffeine, a naturally occurring, bitter-tasting, pharmacologically active secondary compound whose main purpose is to detract herbivores, is also found in lower concentrations in the nectar of some plants, even though nectar, unlike leaves, is made to be consumed by pollinators. [corrected]. A recent laboratory study showed that caffeine may lead to efficient and effective foraging by aiding honeybee memory of a learned olfactory association [4], suggesting that caffeine may enhance bee reward perception. However, without field data, the wider ecological significance of caffeinated nectar remains difficult to interpret. Here we demonstrate in the field that caffeine generates significant individual- and colony-level effects in free-flying worker honeybees. Compared to a control, a sucrose solution with field-realistic doses of caffeine caused honeybees to significantly increase their foraging frequency, waggle dancing probability and frequency, and persistency and specificity to the forage location, resulting in a quadrupling of colony-level recruitment. An agent-based model also demonstrates how caffeine-enhanced foraging may reduce honey storage. Overall, caffeine causes bees to overestimate forage quality, tempting the colony into sub-optimal foraging strategies, which makes the relationship between pollinator and plant less mutualistic and more exploitative. VIDEO ABSTRACT.

Impaired neural reward processing in children and adolescents with reactive attachment disorder: A pilot study.

Reactive attachment disorder (RAD) is characterized by markedly disturbed and developmentally inappropriate social relatedness due to parental maltreatment. RAD patients often display a high number of comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, and certain RAD symptoms are difficult to discriminate from ADHD. One of the core characteristics of ADHD is a decrease in neural reward processing due to dopamine dysfunction. The aim of the present study was to determine whether the brain activity involved in reward processing in RAD patients is impaired in comparison with ADHD patients and typically developed controls. Five RAD patients, 17 typically developed (TD) controls and 17 ADHD patients aged 10-16 years performed tasks with high and low monetary reward while undergoing functional magnetic resonance imaging. ADHD patients were tested before and after 3 months treatment with osmotic release oral system-methylphenidate. Before treatment, ADHD patients showed that striatal and thalamus activities only in the tasks with low monetary reward were lower than TD controls. RAD patients showed decrease in activity of the caudate, putamen and thalamus during both the high and low monetary reward conditions in comparison with all the other groups. In RAD patients, the activity of the putamen was associated with the severity of posttraumatic stress and overt dissociation. Reward sensitivity was markedly decreased in children and adolescents with RAD, as evidenced by a diminished neural response during reward perception. This suggests that dopaminergic dysfunction exists in these patients, and may inform future dopaminergic treatment strategies for RAD.

Offline reactivation of experience-dependent neuronal firing patterns in the rat ventral tegmental area.

In a rest period immediately after a task, neurons in the hippocampus, neocortex, and striatum exhibit spatiotemporal correlation patterns resembling those observed during the task. This reactivation has been proposed as a neurophysiological substrate for memory consolidation. We provide new evidence that rodent ventral tegmental area (VTA) neurons are selective for different types of food stimuli and that stimulus-sensitive neurons strongly reactivate during the rest period following a task that involved those stimuli. Reactivation occurred primarily during slow wave sleep and during quiet awakeness. In these experiments, VTA reactivation patterns were uncompressed and occurred at the firing rate level, rather than on a spike-to-spike basis. Mildly aversive stimuli were reactivated more often than positive ones. The VTA is a pivotal structure involved in the perception and prediction of reward and stimulus salience and is a key neuromodulatory system involved in synaptic plasticity. These results suggest new ways in which dopaminergic signals could contribute to the biophysical mechanisms of selective, system-wide, memory consolidation, and reconsolidation during sleep.

Music and health: what interventions for what results?

Music and health: what interventions for what results?

Septal Glucagon-Like Peptide 1 Receptor Expression Determines Suppression of Cocaine-Induced Behavior.

Glucagon-like peptide 1 (GLP-1) and its receptor GLP-1R are a key component of the satiety signaling system, and long-acting GLP-1 analogs have been approved for the treatment of type-2 diabetes mellitus. Previous reports demonstrate that GLP-1 regulates glucose homeostasis alongside the rewarding effects of food. Both palatable food and illicit drugs activate brain reward circuitries, and pharmacological studies suggest that central nervous system GLP-1 signaling holds potential for the treatment of addiction. However, the role of endogenous GLP-1 in the attenuation of reward-oriented behavior, and the essential domains of the mesolimbic system mediating these beneficial effects, are largely unknown. We hypothesized that the central regions of highest Glp-1r gene activity are essential in mediating responses to drugs of abuse. Here, we show that Glp-1r-deficient (Glp-1r(-/-)) mice have greatly augmented cocaine-induced locomotor responses and enhanced conditional place preference compared with wild-type (Glp-1r(+/+)) controls. Employing mRNA in situ hybridization we located peak Glp-1r mRNA expression in GABAergic neurons of the dorsal lateral septum, an anatomical site with a crucial function in reward perception. Whole-cell patch-clamp recordings of dorsal lateral septum neurons revealed that genetic Glp-1r ablation leads to increased excitability of these cells. Viral vector-mediated Glp-1r gene delivery to the dorsal lateral septum of Glp-1r(-/-) animals reduced cocaine-induced locomotion and conditional place preference to wild-type levels. This site-specific genetic complementation did not affect the anxiogenic phenotype observed in Glp-1r(-/-) controls. These data reveal a novel role of GLP-1R in dorsal lateral septum function driving behavioral responses to cocaine.

Deletion of the GABAA α2-subunit does not alter self administration of cocaine or reinstatement of cocaine seeking

RationaleGABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine.ObjectiveWe investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure.Methodsα2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg).ResultsNo differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not.ConclusionsDespite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking.

Association analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention

BackgroundDopamine receptors are involved in midbrain reward circuit activation. Polymorphisms in two dopamine receptor genes, DRD2 and DRD4, have been associated with altered perception of food reward and weight gain. The objective of this study was to determine whether the same risk alleles were associated with overweight/obesity and with lower reduction of overweight after a 1-year lifestyle intervention.MethodsIn a longitudinal study the association of polymorphisms in DRD2 (rs18000497, risk allele: T, formerly A1 allele at the TaqI A1 polymorphism) and DRD4 (variable number of tandem repeats (VNTR); 48 bp repeat in exon III; risk alleles: 7 repeats or longer: 7R+) was tested on weight loss success following a 1-year lifestyle childhood obesity intervention (OBELDICKS). An additional exploratory cross-sectional case-control study was performed to compare the same DRD polymorphisms in these overweight/obese children and adolescents versus lean adult controls. Subjects were 423 obese and 28 overweight children participating in lifestyle intervention (203 males), age median 12.0 (interquartile range 10.0–13.7) years, body mass index - standard deviation score (BMI-SDS) 2.4 ± 0.5; 583 lean adults (232 males); age median 25.3 (interquartile range 22.5–26.8) years, BMI 19.1 ± 1.9 kg/m2. BMI, BMI-SDS and skinfold thickness measures were assessed at baseline and after 1 year; genotyping was performed for DRD2 risk variant rs1800497 and DRD4 exon III VNTR.ResultsThe DRD2 genotype had a nominal effect on success in the weight loss intervention. The weakest BMI-SDS reduction was in children homozygous for two rs1800497 T-alleles (n = 11) compared to the combined group with zero (n = 308) or one (n = 132) rs1800497 T-allele (-0.08 ± 0.36 vs. -0.28 ± 0.34; p < 0.05). There was no association between the DRD4 VNTR alleles and genotypes and success in the weight loss intervention. No associations of the risk alleles of the DRD2 and DRD4 polymorphisms and obesity were observed in the cross-sectional part of the study.ConclusionsWe did not find association between polymorphisms in DRD2 and DRD4 genes and weight status. However, obese carriers of two DRD2 rs1800497 T-alleles may be at risk for weak responses to lifestyle interventions aimed at weight reduction.Trial registrationObesity intervention program “Obeldicks” is registered at clinicaltrials.gov (NCT00435734).

From Serving in the Military to Serving Loved Ones: Unique Experiences of Older Veteran Caregivers

We examined whether older caregiving veterans differ from noncaregiving veterans in terms of health and psychosocial factors and how these factors and caregiving aspects (i.e., hours, relationship type) relate to caregiving strain and reward. We also evaluated two hypotheses: (1) combat exposure provides protection from emotional caregiving strain, and (2) grandparenting is particularly rewarding. We used a cross-sectional web survey of a nationally representative sample of older veterans in the United States. Data were drawn from the National Health and Resilience in Veterans Study, and participants were 2,025 U.S. veterans aged 60 or older (mean: 71.0; SD: 7.1; range: 60-96). Participants completed measures of caregiving status, sociodemographic characteristics, combat exposure, physical and mental health, cognitive status, and psychosocial characteristics. Caregivers reported caregiving hours, caregiving type, emotional and physical strain, and reward. A total of 20.4% of U.S. older veterans are caregivers. As predicted, among the veteran caregivers, (1) combat exposure was associated with less emotional caregiving strain (odds ratio [OR]: 0.57), and (2) grandparenting was associated with increased perception of caregiving reward (OR: 5.28). Resilience was negatively associated with physical strain, whereas depressive symptoms were associated with greater emotional strain; gratitude, happiness, and social support were additionally associated with greater reward. Caregivers were more likely to be married and highly educated than noncaregivers but did not differ with respect to health or psychosocial characteristics. One in five older U.S. veterans is a caregiver. Older veterans' combat exposure may decrease the emotional demands of caregiving, and grandparenting is perceived as particularly rewarding. Results suggest that older veterans are an important caregiving resource that deserves tailored resources.

Implications of Organisational Culture on Performance of Business Organisations

This article discusses the implications of organizational culture on the performance of business organizations in Nigeria. The first objective of the paper is to elaborate on organisational culture as a determinant of organisational performance. The second objective is to identify four dimensions of African culture as bases for more effective organization culture in the Nigerian context. Works of well known authors in the fields of Culture and Management were reviewed for perspectives and evidence. It is shown from the reviews that a relationship exists between organisational culture and performance of business organisations. In addition, the review suggests that relationship is mediated by reward perception and role perception. Social support, accommodation at work places, religious referencing, supervisor-subordinate age ratio and ethnic diversification are identified as culture factors likely to have positive impact on the performance of business organisations in Nigeria. It is recommended that business organizations in the country should give adequate attention to the development of corporate cultures that integrate the above factors in order to enhance their performance.

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

Reward responsiveness and fatigue in multiple sclerosis

Background: Fatigue is a common symptom in individuals with multiple sclerosis (MS). To date, the pathophysiology of fatigue in MS remains ill-understood; however, converging evidence seems to suggest that a key factor in fatigue development might be the dysregulation of neuropsychological processes underpinning the evaluation of the rewarding outcomes of actions. Objectives: To explore the relationship between reward-related cognition and fatigue in MS and to explore the usefulness of reward perception testing to predict the efficacy of monoamine-modulating drugs on fatigue. Methods: The study included 104 fatigued and 70 fatigue-free Relapsing–Remitting MS patients. All subjects were screened for the lack of any significant mood, cognitive, or personality disorders that could confound results. The different facets of the motivation system such as the patient’s reward perception were assessed at baseline using the Behavioural Inhibition and Behavioural Activation Scales (BIS/BAS). Fatigue was assessed with the Modified Fatigue Impact Scale (MFIS). Fatigue values after three months of therapy with escitalopram or bupropion were correlated with those baseline BIS/BAS scores. Results: Fatigued patients demonstrated lower reward responsiveness compared to fatigue-free subjects. Reward responsiveness scores were found to be associated with baseline MFIS scores and with fatigue reduction after treatment with bupropion: Lower reward responsiveness at baseline predicted higher fatigue remission rates in bupropion-treated patients, as compared with escitalopram-treated patients. Discussion: Reward responsiveness was linked with MS-related fatigue and might represent one of its key cognitive underpinnings. Our results suggest that evaluation of reward responsiveness could provide useful information to guide individualized therapy of MS-related fatigue.

Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

BackgroundThere are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour.ObjectiveWe designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk.Design/MethodsTwenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%.ResultsSubjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a ‘risk premium’ of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability.ConclusionsThis simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia.

Neuronal Responses in the Nucleus Accumbens Shell during Sexual Behavior in Male Rats

Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward-related processing, and the inhibition of sexual behavior after ejaculation.

Functional Neuroimaging in Craniopharyngioma: A Useful Tool to Better Understand Hypothalamic Obesity?

Objective: To use functional magnetic resonance imaging (fMRI) in craniopharyngioma (CP) patients to examine the hypothesis that hypothalamic damage due to CP and its treatment results in enhanced perception of food reward and/or impaired central satiety processing. Methods: Pre- and post-meal responses to visual food cues in brain regions of interest (ROI; bilateral nucleus accumbens, bilateral insula, and medial orbitofrontal cortex) were assessed in 4 CP patients versus 4 age- and weight-matched controls. Stimuli consisted of images of high- (‘fattening’) and low-calorie (‘non-fattening’) foods in blocks, alternating with non-food object blocks. After the first fMRI scan, subjects drank a high-calorie test meal to suppress appetite, then completed a second fMRI scan. Within each ROI, we calculated mean z-scores for activation by fattening as compared to non-fattening food images. Results: Following the test meal, controls showed suppression of activation by food cues while CP patients showed trends towards higher activation. Conclusion: These data, albeit in a small group of patients, support our hypothesis that perception of food cues may be altered in hypothalamic obesity (HO), especially after eating, i.e. in the satiated state. The fMRI approach is encouraging for performing future mechanistic studies of the brain response to food cues and satiety in patients with hypothalamic or other forms of childhood obesity.

The rewarding and locomotor-sensitizing effects of repeated cocaine administration are distinct and separable in mice

Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor-stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception.