Palatable Food Reward Research Articles

GLP-1/dexamethasone inhibits food reward without inducing mood and memory deficits in mice

BackgroundPharmacotherapies targeting motivational aspects of feeding and palatable food reward, while sparing mood and cognitive function, represent an alluring approach to reverse obesity and maintain weight loss in an obesogenic environment. A novel glucagon-like peptide-1/dexamethasone (GLP-1/Dexa) conjugate, developed to selectively activate glucocorticoid receptors in GLP-1 receptor-expressing cells was shown to decrease food intake and lower body weight in obese mice. Here, we investigate if this novel drug candidate modulates the rewarding properties of food and if it affects behavioral indices of mood and memory. MethodsC57Bl6 mice treated with the GLP-1/Dexa conjugate, GLP-1 or vehicle lever-pressed for high-fat, high sugar (HFHS) food rewards in an operant task. Alterations in food-motivated behavior were also assessed following a HFHS diet withdrawal manipulation (switch to chow). The effects of repeated GLP-1/Dexa conjugate, GLP-1 or vehicle on free-feeding intake, body weight, anxiodepressive behaviors (elevated-plus maze, open field test & forced swim test), memory (novel object recognition) and mRNA expression of reward-relevant markers in the nucleus accumbens were also evaluated in mice fed a HFHS diet for 12 weeks. ResultsMice treated with a GLP-1 analogue displayed a transient (4 h) reduction in their motivation to lever press for HFHS reward, whereas treatment with equimolar doses of GLP-1/Dexa delivered a superior and sustained (20 h) suppression of food-motivated behavior. GLP-1/Dexa also inhibited food reward following withdrawal from the HFHS diet. These benefits coincided with related transcriptional changes of dopaminergic markers in the nucleus accumbens. Importantly, repeated GLP-1/Dexa treatment during a HFHS diet caused weight loss without affecting anxiodepressive behavior and memory. ConclusionVia its actions to blunt the rewarding effects of palatable food without affecting mood and recognition memory, GLP-1-directed targeting of dexamethasone may serve as a promising and safe anti-obesity strategy.

Ghrelin's effects on food motivation in rats are not limited to palatable foods.

The “hunger” hormone, ghrelin, is powerfully orexigenic. Even in the absence of hunger, ghrelin delivery to rats increases consumption of chow, as well as palatable foods, and increases motivated behaviour for palatable food rewards. Inspired by the finding that ghrelin increases the selection of chow in rats offered a choice diet (lard, sucrose or chow) and even in rats bingeing on a high‐fat diet, we aimed to explore whether the effects of ghrelin on motivation extend to regular chow. Rats were conditioned to lever press for either chow or sucrose pellets in a progressive ratio (PR) operant conditioning task. The effect of acute i.c.v. delivery of ghrelin on both chow and sucrose self‐administration was determined and compared with overnight fasting (ie, when endogenous ghrelin levels are elevated). We found that ghrelin similarly increased motivated behaviour for chow and sucrose pellets. The effect of fasting on motivated behaviour for both food pellets was comparable in magnitude to that induced by ghrelin, albeit with an earlier ceiling effect during the PR session. Devaluation experiments (in which rats are offered either food reinforcer in excess prior to PR testing) did not support the hypothesis that sucrose pellets would be more difficult to devalue (as a result of their higher incentive value) than chow pellets. When exchanging the respective pellets during a PR session, chow‐conditioned rats were more motivated for sucrose pellets compared to chow pellets; however, sucrose‐conditioned rats were similarly motivated for chow pellets compared to sucrose pellets. Thus, using sucrose as a reward may increase the motivation even for less palatable foods. We conclude that the impact of ghrelin on food‐motivated behaviour in fed rats is not limited to palatable foods but extends to regular chow, and also that the magnitude of the effect is considerable compared to that of an overnight fast.

Exploring preferences for variable delays over fixed delays to high-value food rewards as a model of food-seeking behaviours in humans.

Foraging and operant models suggest that animals will tolerate uncertainty or risk to obtain food quickly. In modern food environments, sustained access to quick energy-dense foods can promote weight gain. Here, we used a discrete-choice procedure to examine peoples' decisions about when next to eat high-value, palatable food rewards, probabilistically delivered immediately or following longer delays. In Experiment 1, moderately hungry young females showed consistent preferences for a variable delay option that delivered food rewards immediately or following long delays over a fixed delay option that delivered the same rewards following intermediate delays. These preferences were stronger in females with higher BMIs compared with lower BMIs, suggesting that quick food can enhance the value of uncertain or 'risky' food-seeking strategies in individuals vulnerable to future weight gain. In Experiment 2, prior exposure to a subtle and not easily identifiable food aroma increased selections of the variable delay option following delayed food rewards in a mixed sample of male and female adults, providing preliminary evidence that food cues can sustain uncertain food-seeking strategies. These data highlight a working hypothesis that the rapid delivery and consumption of food rewards, and food cues, can increase risk-tolerance in the food-seeking behaviours of individuals who are vulnerable to weight gain. This article is part of the theme issue 'Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications'.

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities

The mu opioid receptor (MOR) plays a critical role in modulating social behavior in humans and animals. Accordingly, MOR null mice display severe alterations in their social repertoire as well as multiple other behavioral deficits, recapitulating core and secondary symptoms of autism spectrum disorder (ASD). Such behavioral profile suggests that MOR dysfunction, and beyond this, altered reward processes may contribute to ASD etiopathology. Interestingly, the only treatments that proved efficacy in relieving core symptoms of ASD, early behavioral intervention programs, rely principally on positive reinforcement to ameliorate behavior. The neurobiological underpinnings of their beneficial effects, however, remain poorly understood. Here we back-translated applied behavior analysis (ABA)-based behavioral interventions to mice lacking the MOR (Oprm1−/−), as a model of autism with blunted reward processing. By associating a positive reinforcement, palatable food reward, to daily encounter with a wild-type congener, we were able to rescue durably social interaction and preference in Oprm1−/− mice. Along with behavioral improvements, the expression of marker genes of neuronal activity and plasticity as well as genes of the oxytocin/vasopressin system were remarkably normalized in the reward/social circuitry. Our study provides further evidence for a critical involvement of reward processes in driving social behavior and opens new perspectives regarding therapeutic intervention in ASD.

Activation of medial hypothalamic orexin neurons during a Go/No-Go task

Orexin neurons (Orx; also referred to as hypocretin) are found exclusively in the hypothalamus, and release the neuropeptides orexin A and orexin B (also referred to as hypocretin 1 and 2) throughout the CNS. With its widespread targets, the orexin system is involved in a number of functions including, but not limited to stress, reward, wakefulness, and food seeking. Our laboratory has previously proposed that the dorsomedial hypothalamus (DMH) and perifornical (PFA) orexin neurons function in stress and arousal whereas those in lateral hypothalamus (LH) participate in reward processes (Harris and Aston-Jones, 2006). In the current study, we compared Fos activation in orexin neurons located in medial hypothalamus (DMH and PFA) to those in LH during a Go/No-Go task for a highly palatable food reward, a task that would likely activate regions for arousal/attention as well as reward. The Go/No-Go paradigm is a useful behavioral tool to measure behavioral inhibition, impulsivity, learning, and reaction time. Our results revealed increased activation of medial hypothalamic orexin neurons correlated with greater accuracy on the Go/No-Go task. No correlation was found between Go/No-Go accuracy and activation of lateral hypothalamic orexin neurons. This study supports a functional dichotomy of medial vs lateral orexin neurons, and indicates a role for medial orexin neurons in behavioral performance that requires response inhibition.

Drug Seeking and Relapse: New Evidence of a Role for Orexin and Dynorphin Co-transmission in the Paraventricular Nucleus of the Thalamus.

The long-lasting vulnerability to relapse remains the main challenge for the successful treatment of drug addiction. Neural systems that are involved in processing natural rewards and drugs of abuse overlap. However, neuroplasticity that is caused by drug exposure may be responsible for maladaptive, compulsive, and addictive behavior. The orexin (Orx) system participates in regulating numerous physiological processes, including energy metabolism, arousal, and feeding, and is recruited by drugs of abuse. The Orx system is differentially recruited by drugs and natural rewards. Specifically, we found that the Orx system is more engaged by drugs than by non-drugs, such as sweetened condensed milk (SCM) or a glucose saccharin solution (GSS), in an operant model of reward seeking. Although stimuli (S+) that are conditioned to cocaine (COC), ethanol, and SCM/GSS equally elicited reinstatement, Orx receptor blockade reversed conditioned reinstatement for drugs vs. non-drugs. Moreover, the hypothalamic recruitment of Orx cells was greater in rats that were tested with the COC S+ vs. SCM S+, indicating of a preferential role for the Orx system in perseverative, compulsive-like COC seeking and not behavior that is motivated by palatable food. Accumulating evidence indicates that the paraventricular nucleus of the thalamus (PVT), which receives major Orx projections, mediates drug-seeking behavior. All Orx neurons contain dynorphin (Dyn), and Orx and Dyn are co-released. In the VTA, they play opposing roles in reward and motivation. To fully understand the physiological and behavioral roles of Orx transmission in the PVT, one important consideration is that Orx neurons that project to the PVT may co-release Orx with another peptide, such as Dyn. The PVT expresses both Orx receptors and κ opioid receptors, suggesting that Orx and Dyn act in tandem when released in the PVT, in addition to the VTA. The present review discusses recent findings that suggest the maladaptive recruitment of Orx/Dyn-PVT neurotransmission by drugs of abuse vs. a highly palatable food reward.

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder.

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value. Cue reactivity, the sensitivity to cues previously linked with the drug-taking experience, plays a prominent role in human craving during abstinence. Cue reactivity can be assessed as the attentional orientation toward drug-associated cues that is measurable as appetitive approach behavior in both preclinical and human studies. Herein describes an assessment of cue reactivity in rats trained to self-administer cocaine. Cocaine self-administration is paired with the presentation of discrete cues that act as conditioned reinforcers (i.e., house light, stimulus light, infusion pump sounds). Following a period of abstinence, lever presses in the cocaine self-administration context accompanied by the discrete cues previously paired with cocaine infusion are measured as cue reactivity. This model is useful to explore neurobiological mechanisms underlying cue reactivity processes as well as to assess pharmacotherapies to suppress cue reactivity and therefore, modify relapse vulnerability. Advantages of the model include its translational relevance, and its face and predictive validities.The primary limitation of the model is that the cue reactivity task can only be performed infrequently and must only be used in short duration (e.g., 1 hour), otherwise rats will begin to extinguish the pairing of the discrete cues with the cocaine stimulus. The model is extendable to any positively reinforcing stimulus paired with discrete cues; though particularly applicable to drugs of abuse, this model may hold future applications in fields such as obesity, where palatable food rewards can act as positively reinforcing stimuli.

Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats.

The hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration. Chronic Hcrt silencing did not impact cocaine self-administration under short-access conditions, but robustly attenuated cocaine intake under extended access conditions, a model that mimics key features of compulsive cocaine taking. In addition, Hcrt silencing decreased motivation for both cocaine and a highly palatable food reward (i.e., sweetened condensed milk; SCM) under a progressive ratio schedule of reinforcement, but did not alter responding for SCM under a fixed ratio schedule. Importantly, Hcrt silencing did not affect food or water consumption, and had no consequence for general measures of arousal and stress reactivity. At the molecular level, chronic Hcrt knockdown reduced the number of neurons expressing dynorphin (DYN), and to a smaller extent melanin-concentrating hormone (MCH), in the dorsal hypothalamus. These original findings support the hypothesis that HCRT neurotransmission promotes operant responding for both drug and non-drug rewards, preferentially under conditions requiring a high degree of motivation. Furthermore, the current study provides compelling evidence for the involvement of the HCRT system in cocaine self-administration also under low-effort conditions in rats allowed extended access, possibly via functional interactions with DYN and MCH signaling.

Phencyclidine increased while isolation rearing did not affect progressive ratio responding in rats: Investigating potential models of amotivation in schizophrenia

BackgroundSchizophrenia is a debilitating neurodevelopmental disorder affecting 1% of the global population with heterogeneous symptoms including positive, negative, and cognitive. While treatment for positive symptoms exists, none have been developed to treat negative symptoms. Animal models of schizophrenia are required to test targeted treatments and since patients exhibit reduced effort (breakpoints) for reward in a progressive ratio (PR) task, we examined the PR breakpoints of rats treated with the NMDA receptor antagonist phencyclidine or those reared in isolation – two common manipulations used to induce schizophrenia-relevant behaviors in rodents. MethodsIn two cohorts, the PR breakpoint for a palatable food reward was examined in Long Evans rats after: 1) a repeated phencyclidine regimen; 2) A subchronic phencyclidine regimen followed by drug washout; and 3) post-weaning social isolation. ResultsRats treated with repeated phencyclidine and those following washout from phencyclidine exhibited higher PR breakpoints than vehicle-treated rats. The breakpoint of isolation reared rats did not differ from those socially reared, despite abnormalities of these rats in other schizophrenia-relevant behaviors. ConclusionDespite their common use for modeling other schizophrenia-relevant behaviors neither phencyclidine treatment nor isolation rearing recreated the motivational deficits observed in patients with schizophrenia, as measured by PR breakpoint. Other manipulations, and negative symptom-relevant behaviors, require investigation prior to testing putative therapeutics.

Persistent cognitive and morphological alterations induced by repeated exposure of adolescent rats to the abused inhalant toluene

While thepsychoactive inhalant toluene causes behavioral effects similarto those produced by other drugs of abuse, the persistent behavioral and anatomical abnormalities induced by toluene exposure are not well known. To mimic human “binge-like“ inhalant intoxication, adolescent, male Sprague-Dawley rats were exposed to toluene vapor (5700ppm) twice daily for five consecutive days. These rats remained in their home cages until adulthood (P60), when they were trained in operant boxes to respond to a palatable food reward and then challenged with several different cognitive tasks. Rats that experienced chronic exposure to toluene plus abstinence (“CTA”) showed enhanced performance in a strategy set-shifting task using a between-session, but not a within-session test design. CTA also blunted operant and classical conditioning without affecting responding during a progressive ratio task. While CTA rats displayed normal latent inhibition, previous exposure to a non-reinforced cue enhanced extinction of classically conditioned approach behavior of these animals compared to air controls. To determine whether CTA alters the structural plasticity of brain areas involved in set-shifting and appetitive behaviors, we quantified basal dendritic spine morphology in DiI-labeled pyramidal neurons in layer 5 of the medial prefrontal cortex (mPFC) and medium spiny neurons in the nucleus accumbens (NAc). There were no changes in dendritic spine density or subtype in the mPFC of CTA rats while NAc spine density was significantly increased due to an enhanced prevalence of long-thin spines. Together, these findings suggest that the persistent effects of CTA on cognition are related to learning and memory consolidation/recall, but not mPFC-dependent behavioral flexibility.

Preliminary evidence of sex differences in behavioral and neural responses to palatable food reward in rats

The female bias in eating disorder prevalence is the largest in all of psychiatry. Binge eating on palatable food (PF) is a core, maladaptive symptom that cuts across all major types of eating disorders and can be studied via animal models. Using an individual differences rat model of binge eating that identifies binge eating prone (BEP) and binge eating resistant (BER) phenotypes, we previously showed that, compared with males, females consume more PF and are more likely to be classified as BEP. One potential explanation for this sex difference is that PF is inherently more rewarding to females, leading to higher rates of binge eating. Here we tested the hypothesis that females have more robust behavioral and neural responses to PF reward than males. Adult male (N=18) and female (N=17) Sprague-Dawley rats were exposed to the Conditioned Place Preference paradigm using PF as the unconditioned stimulus. Select males (N=9) and females (N=9) were video-recorded during three of the PF-paired conditioning sessions to score feeding behavior. Following CPP, 13 male and 12 female rats were exposed to PF just prior to sacrifice to induce expression of the neural activation marker Fos, and Fos expression was quantified in mesocorticolimbic, hypothalamic, and amygdalar circuits. In the CPP paradigm, females displayed a more robust shift in preference for the chamber paired with PF compared with males, and behavioral analyses revealed that average duration of individual feeding bouts during pairing sessions was longer in females than in males. Fos expression was significantly higher in females vs. males in select regions of the mesocorticolimbic reward circuit, with no sex differences in hypothalamic or amygdalar regions. These results provide initial evidence that PF may be more rewarding to females than to males, possibly due to heightened responsiveness of neural substrates that mediate the hedonic and motivational responses to PF, which in part, may underlie sex differences in binge eating proneness.

Intermittent feeding alters sensitivity to changes in reward value

The influence of binge-like feeding schedules on subsequent food-related behavior is not well understood. We investigated the effect of repeated cycles of restriction and refeeding on two food-related behaviors; goal-directed responding for a palatable food reward and sensory-specific satiety. Hungry rats were trained to perform two instrumental actions for two distinct food outcomes and were then subjected to repeated cycles of restricted and unrestricted access to their maintenance chow for 30-days or were maintained on food restriction. Goal-directed control was then assessed using specific satiety-induced outcome devaluation. Rats were given 1 h access to one of theoutcomes and were then immediately given a choice between the two actions. Rats maintained on restriction responded more for the valued than the devalued reward but rats with a history of restriction and refeeding failed to show this effect. Importantly, all rats showed sensory-specific satiety when offered a choice between the two foods, indicating that pre-feeding selectively reduced the value of the pre-fed food. By contrast, sensory-specific satiety was not observed in rats with a history of intermittent feeding when the foods were offered sequentially. These results indicate that, similar to calorically dense diets, intermittent feeding patterns can impair the performance of goal-directed actions as well as the ability to reject a pre-fed food when it is offered alone.

Food Seeking in a Risky Environment: A Method for Evaluating Risk and Reward Value in Food Seeking and Consumption in Mice.

Most studies that measure food intake in mice do so in the home cage environment. This necessarily means that mice do not engage in food seeking before consumption, a behavior that is ubiquitous in free-living animals. We modified and validated several commonly used anxiety tests to include a palatable food reward within the anxiogenic zone. This allowed us to assess risk-taking behavior in food seeking in mice in response to different metabolic stimuli. We modified the open field test and the light/dark box by placing palatable peanut butter chips within a designated food zone inside the anxiogenic zone of each apparatus. We then assessed parameters of the interaction with the food reward. Fasted mice or mice treated with ghrelin showed increased consumption and increased time spent in the food zone immediately around the food reward compared to ad libitum fed mice or mice treated with saline. However, fasted mice treated with IP glucose before exposure to the behavioral arena showed reduced time in the food zone compared to fasted controls, indicating that acute metabolic signals can modify the assessment of safety in food seeking in a risky environment. The tests described in this study will be useful in assessing risk processing and incentive salience of food reward, which are intrinsic components of food acquisition outside of the laboratory environment, in a range of genetic and pharmacological models.

Differential role of hypothalamic orexin/hypocretin neurons in reward seeking motivated by cocaine versus palatable food

Hypothalamic orexin/hypocretin (Orx/Hcrt) neurons are thought to mediate both food-reinforced behaviors and behavior motivated by drugs of abuse. However, the relative role of the Orx/Hcrt system in behavior motivated by food versus drugs of abuse remains unclear. This investigation addressed this question by contrasting hypothalamic Orx/Hcrt neuronal activation associated with reinstatement of reward seeking induced by stimuli conditioned to cocaine (COC) versus highly palatable food reward, sweetened condensed milk (SCM). Orx/Hcrt neuronal activation in the lateral hypothalamus, dorsomedial hypothalamus and perifornical area, determined by dual c-fos/orx immunocytochemistry, was quantified in rat brains, following reinstatement of reward seeking induced by a discriminative stimulus (S+ ) conditioned to COC or SCM. The COC S+ and SCM S+ initially produced the same magnitude of reward seeking. However, over four subsequent tests, behavior induced by the SCM S+ decreased to extinction levels, whereas reinstatement induced by the COC S+ perseverated at undiminished levels. Following both the first and fourth tests, the percentage of Orx/Hcrt cells expressing Fos was significantly increased in all hypothalamic subregions in rats tested with the COC S+ but not rats tested with the SCM S+ . These findings point toward a role for the Orx/Hcrt system in perseverating, compulsive-like COC seeking but not behavior motivated by palatable food. Moreover, analysis of the Orx/Hcrt recruitment patterns suggests that failure of Orx/Hcrt neurons in the lateral hypothalamus to respond to inhibitory inputs from Orx/Hcrt neurons in the dorsomedial hypothalamus/perifornical area may contribute to the perseverating nature of COC seeking.

Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele.

Because no large prospective study has investigated neural vulnerability factors that predict future weight gain we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. Elevated reward activation in response to food cues predicted future body fat gain. Elevated reward response to food receipt predicted body fat gain for adolescents with a TaqIA A2/A2 allele and lower reward response predicted body fat gain for those with a TaqIA A1 allele. Results imply that too much or too little dopamine signaling and reward region responsivity increases risk for overeating.

Effects of Prior Cocaine Versus Morphine or Heroin Self-Administration on Extinction Learning Driven by Overexpectation Versus Omission of Reward

BackgroundAddiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here, we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward overexpectation. MethodsIn experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hours per day (limited access). In experiment 2, we trained rats to self-administer heroin or sucrose for 12 hours per day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the overexpectation procedure and later by omitting the food reward. ResultsRats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both overexpectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to overexpectation. ConclusionsHere we show that cocaine and heroin can induce long-lasting deficits in the ability to extinguish reward seeking. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of overexpectation.

Anticipatory and foraging behaviors in response to palatable food reward in chickens: Effects of dopamine D2 receptor blockade and domestication

Behaviors associated with anticipation and search for palatable food may provide information about dopaminergic reward processes and positive motivational affect in animals. The overall aim was to investigate the involvement of dopamine signaling in the regulation of cue-induced anticipation and search for palatable food reward in chicken, and whether domestication has affected expression of reward-related behaviors. The specific aims were to describe effects of mealworms (palatable food for hens) and haloperidol (a dopamine D2 antagonist) on foraging behaviors and cue-induced anticipatory behaviors in Red Junglefowl (RJF; the wild ancestor of modern laying hens) and a white layer hybrid (LSL). RJF (n=26) and LSL (n=20) were initially trained on a conditioning schedule to anticipate mealworms (unconditioned stimulus; US) 25s after exposure to a red light (conditioned stimulus; CS). For the experiment, hens received haloperidol or saline injections 30min before exposure to one CS+US combination. Behavior was registered 10min before CS and 10min after US (foraging behaviors), and during the CS–US interval (anticipatory behaviors). Higher frequencies of CS-induced anticipatory head movements, faster approach to rewards, and higher frequency of foraging behaviors were found in LSL compared to RJF. Haloperidol suppressed CS-induced head movements in both breeds, and the frequency of foraging behaviors after reward delivery. The results support a role of dopamine signaling in the regulation of reward processes in chickens, and suggest that domestication has changed the threshold for perceiving food incentives and/or for expressing reward-related behaviors that may be indicative of positive motivational affect in hens.

The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex-the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing.

Generating positive affective states in sheep: The influence of food rewards and opioid administration

This study investigated the involvement of the opioid system in modulating the affective state after the consumption of palatable and unpalatable rewards, using judgement bias as an indicator of the affective state. We hypothesised that consuming a palatable food reward would generate a more optimistic bias compared to receiving unpalatable wood chips. We hypothesised that morphine administration would further enhance the optimistic judgement bias after consumption of a food reward while reducing a pessimistic bias after receiving wood chips. Naloxone administration was expected to prevent the formation of an optimistic bias after consumption of a food reward, and was expected to have little effect after receiving the wood chips. The judgement bias arena consisted of a positive and a negative location cue, associated with conspecifics and a dog, respectively, as well as three non-reinforced ambiguous location cues between the positive and negative locations. Thirty sheep were successfully trained to approach the conspecifics and avoid the dog. Following training, sheep were randomly assigned to one of three treatments; morphine (1mg/kg), naloxone (2mg/kg) and control. Within each treatment, half the ewes received a small food reward and the other half wood chips before exposure to each of the five locations. Judgement bias was assessed by recording the latency to approach the five locations. Animals receiving the food reward approached the locations faster than animals receiving the wood chips (0.83±0.04 and 1.00±0.04 log-transformed latencies (s), respectively, P<0.01). The latency was also near-significantly affected by a treatment×reward type interaction (P=0.05), mostly due to the morphine treated ewes approaching the locations faster after receiving the food reward (log-transformed latencies (s): 0.82±0.07 for control sheep after consuming food, 0.71±0.07 for morphine treated sheep after food, 0.96±0.07 for naloxone treated sheep after food, 0.94±0.07 for control sheep after wood chips, 1.07±0.07 for morphine sheep after wood chips and 1.00±0.07 for naloxone sheep after wood chips). These results show that consumption of a food reward induced an optimistic judgement bias and suggest that morphine administration further enhanced this optimistic judgement bias. However, animal numbers and statistical power were low in this experiment and further research is necessary to confirm whether the opioid system is involved in the formation of judgement biases.

Leptin Signaling in the Medial Nucleus Tractus Solitarius Reduces Food Seeking and Willingness to Work for Food

The adipose-derived hormone leptin signals in the medial nucleus tractus solitarius (mNTS) to suppress food intake, in part, by amplifying within-meal gastrointestinal (GI) satiation signals. Here we show that mNTS leptin receptor (LepRb) signaling also reduces appetitive and motivational aspects of feeding, and that these effects can depend on energy status. Using the lowest dose that significantly suppressed 3-h cumulative food intake, unilateral leptin (0.3 μg) administration to the mNTS (3 h before testing) reduced operant lever pressing for sucrose under increasing work demands (progressive ratio reinforcement schedule) regardless of whether animals were energy deplete (food restricted) or replete (ad libitum fed). However, in a separate test of food-motivated responding in which there was no opportunity to consume food (conditioned place preference (CPP) for an environment previously associated with a palatable food reward), mNTS leptin administration suppressed food-seeking behavior only in chronically food-restricted rats. On the other hand, mNTS LepRb signaling did not reduce CPP expression for morphine reinforcement regardless of energy status, suggesting that mNTS leptin signaling differentially influences motivated responding for food vs opioid reward. Overall results show that mNTS LepRb signaling reduces food intake and appetitive food-motivated responding independent of energy status in situations involving orosensory and postingestive contact with food, whereas food-seeking behavior independent of food consumption is only reduced by mNTS LepRb activation in a state of energy deficit. These findings reveal a novel appetitive role for LepRb signaling in the mNTS, a brain region traditionally linked with processing of meal-related GI satiation signals.