The coding of valence and identity in the mammalian taste system.

The ability of the taste system to identify a tastant (what it tastes like) enables animals to recognize and discriminate between the different basic taste qualities1,2. The valence of a tastant (whether it is appetitive or aversive) specifies its hedonic value and elicits the execution of selective behaviours. Here we examine how sweet and bitter are afforded valence versus identity in mice. We show that neurons in the sweet-responsive and bitter-responsive cortex project to topographically distinct areas of the amygdala, with strong segregation of neural projections conveying appetitive versus aversive taste signals. By manipulating selective taste inputs to the amygdala, we show that it is possible to impose positive or negative valence on a neutral water stimulus, and even to reverse the hedonic value of a sweet or bitter tastant. Remarkably, mice with silenced neurons in the amygdala no longer exhibit behaviour that reflects the valence associated with direct stimulation of the taste cortex, or with delivery of sweet and bitter chemicals. Nonetheless, these mice can still identify and discriminate between tastants, just as wild-type controls do. These results help to explain how the taste system generates stereotypic and predetermined attractive and aversive taste behaviours, and support the existence of distinct neural substrates for the discrimination of taste identity and the assignment of valence.

The olfactory basis of orchid pollination by mosquitoes.

Mosquitoes are important vectors of disease and require sources of carbohydrates for reproduction and survival. Unlike host-related behaviors of mosquitoes, comparatively less is understood about the mechanisms involved in nectar-feeding decisions, or how this sensory information is processed in the mosquito brain. Here we show that Aedes spp. mosquitoes, including Aedes aegypti, are effective pollinators of the Platanthera obtusata orchid, and demonstrate this mutualism is mediated by the orchid's scent and the balance of excitation and inhibition in the mosquito's antennal lobe (AL). The P. obtusata orchid emits an attractive, nonanal-rich scent, whereas related Platanthera species-not visited by mosquitoes-emit scents dominated by lilac aldehyde. Calcium imaging experiments in the mosquito AL revealed that nonanal and lilac aldehyde each respectively activate the LC2 and AM2 glomerulus, and remarkably, the AM2 glomerulus is also sensitive to N,N-diethyl-meta-toluamide (DEET), a mosquito repellent. Lateral inhibition between these 2 glomeruli reflects the level of attraction to the orchid scents. Whereas the enriched nonanal scent of P. obtusata activates the LC2 and suppresses AM2, the high level of lilac aldehyde in the other orchid scents inverts this pattern of glomerular activity, and behavioral attraction is lost. These results demonstrate the ecological importance of mosquitoes beyond operating as disease vectors and open the door toward understanding the neural basis of mosquito nectar-seeking behaviors.

A volatilized pyrethroid insecticide from a mosquito repelling device does not impact honey bee foraging and recruitment.

Because nontarget, beneficials, like insect pollinators, may be exposed unintentionally to insecticides, it is important to evaluate the impact of chemical controls on the behaviors performed by insect pollinators in field trials. Here we examine the impact of a portable mosquito repeller, which emits prallethrin, a pyrethroid insecticide, on honey bee foraging and recruitment using a blinded, randomized, paired, parallel group trial. We found no significant effect of the volatilized insecticide on foraging frequency (our primary outcome), waggle dance propensity, waggle dance frequency, and feeder persistency (our secondary outcomes), even though an additional deposition study confirmed that the treatment device was performing appropriately. These results may be useful to consumers that are interested in repelling mosquitos, but also concerned about potential consequences to beneficial insects, such as honey bees.

Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice.

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.

Dopamine, behavior, and addiction.

Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning-long-term potentiation (LTP)-of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking-or "pacemaker firing"-of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.

Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats.

Opioid use disorder (OUD) causes the death of nearly 130 Americans daily. It is evident that new avenues for treatment are needed. To this end, studies have reported that 'satiety' agents such as the glucagon-like peptide-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), decreases responding for addictive drugs such as cocaine, nicotine, alcohol, and oxycodone, but no work has been done with heroin. In this study, we used a reward devaluation model in which rats avoid ingesting a saccharin solution that predicts drug availability to test the effects of 2.4 µg/kg Ex-4 on responding for a natural reward cue (i.e., saccharin) and on cue- and drug-induced heroin seeking. The results showed that treatment with Ex-4 during the 16-day abstinence period and on the test day decreased cue-induced heroin seeking. Drug-induced heroin seeking also was reduced by Ex-4, but only when using a 1 h, but not a 6 h, pretreatment time. Treatment with Ex-4 did not alter intake of the saccharin cue when the drug was on board, but a history of treatment with Ex-4 increased acceptance of the saccharin cue in later extinction trials. Finally, treatment with Ex-4 did not alter body weight, but was associated with increased Orexin 1 receptor (OX1) mRNA expression in the nucleus accumbens shell. Taken together, these findings are the first to show that treatment with a GLP-1R agonist can reduce both cue-induced seeking and drug-induced reinstatement of heroin seeking. As such, a GLP-1R agonist may serve as an effective treatment for OUD in humans.

Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues in male rats.

Oxytocin potently reduces food intake and is a potential target system for obesity treatment. A better understanding of the behavioral and neurobiological mechanisms mediating oxytocin's anorexigenic effects may guide more effective obesity pharmacotherapy development. The present study examined the effects of central (lateral intracerebroventricular [ICV]) administration of oxytocin in rats on motivated responding for palatable food. Various conditioning procedures were employed to measure distinct appetitive behavioral domains, including food seeking in the absence of consumption (conditioned place preference expression), impulsive responding for food (differential reinforcement of low rates of responding), effort-based appetitive decision making (high-effort palatable vs. low-effort bland food), and sucrose reward value encoding following a motivational shift (incentive learning). Results reveal that ICV oxytocin potently reduces food-seeking behavior, impulsivity, and effort-based palatable food choice, yet does not influence encoding of sucrose reward value in the incentive learning task. To investigate a potential neurobiological mechanism mediating these behavioral outcomes, we utilized in vivo fiber photometry in ventral tegmental area (VTA) dopamine neurons to examine oxytocin's effect on phasic dopamine neuron responses to sucrose-predictive Pavlovian cues. Results reveal that ICV oxytocin significantly reduced food cue-evoked dopamine neuron activity. Collectively, these data reveal that central oxytocin signaling inhibits various obesity-relevant conditioned appetitive behaviors, potentially via reductions in food cue-driven phasic dopamine neural responses in the VTA.

Dissociation of Appetitive Overexpectation and Extinction in the Infralimbic Cortex.

Behavioral change is paramount to adaptive behavior. Two ways to achieve alterations in previously established behavior are extinction and overexpectation. The infralimbic (IL) portion of the medial prefrontal cortex controls the inhibition of previously established aversive behavioral responses in extinction. The role of the IL cortex in behavioral modification in appetitive Pavlovian associations remains poorly understood. Here, we seek to determine if the IL cortex modulates overexpectation and extinction of reward learning. Using overexpectation or extinction to achieve a reduction in behavior, the present findings uncover a dissociable role for the IL cortex in these paradigms. Pharmacologically inactivating the IL cortex left overexpectation intact. In contrast, pre-training manipulations in the IL cortex prior to extinction facilitated the reduction in conditioned responding but led to a disrupted extinction retrieval on test drug-free. Additional studies confirmed that this effect is restricted to the IL and not dependent on the dorsally-located prelimbic cortex. Together, these results show that the IL cortex underlies extinction but not overexpectation-driven reduction in behavior, which may be due to regulating the expression of conditioned responses influenced by stimulus-response associations rather than stimulus-stimulus associations.

The effects of a GLP-1 analog liraglutide on reward value and the learned inhibition of appetitive behavior in male and female rats.

Liraglutide, a relatively long-lasting analog of glucagon-like peptide-1 (GLP-1), has received recent attention as a treatment for obesity. It has been proposed that activation of GLP-1 receptors in mesolimbic reward pathways contributes to this outcome by reducing hedonic value of food. However, other findings suggest that activation of GLP-1 signaling pathways may suppress appetitive behavior by enhancing a hippocampal-dependent form of learned inhibition. The present experiment compares these two alternatives. Rats first solved a hippocampal-dependent discrimination problem in which a target stimulus signaled the delivery of sucrose, except when it was preceded by an inhibitory cue that signaled nonreward. The effects of 12 daily intraperitoneal (i.p.) injections of liraglutide on responding to the target cue was then compared with and without the inhibitory stimulus. Relative to saline, liraglutide suppressed responding to the target cue only on trials when the inhibitory stimulus was also present (p < .05). This outcome was independent of sex and maintenance diet (Western diet or standard chow). The failure of liraglutide to suppress responding in the absence of the inhibitory cue argues against the notion that this GLP-1 agonist reduced the value of food reward and favors the idea that it enhanced a hippocampal-dependent form of behavioral inhibition.

Effects of ovarian hormones on the emission of 50-kHz ultrasonic vocalizations during distributed clitoral stimulation in the rat.

Fifty-kHz ultrasonic vocalizations (USVs) are emitted by adult rats during appetitive phases of behavior in response to stimuli thought to be associated with a positive affective state. In particular, 50-kHz USVs with rapid frequency oscillations, known as trills and flat-trills, in which these oscillations are flanked by a monotonic portion, are together positively correlated with appetitive behaviors such as rough and tumble play, drug and natural reward, and mating. Female rats produce 50-kHz USVs during a variety of sexual contexts, yet data are still vague as female sexual behavior is seldom studied on its own. Distributed clitoral stimulation (CLS) offers a unique approach to investigating female 50-kHz USVs as it mimics stimulation received during mating. Although CLS induces a sexual reward state, it is unknown whether CLS elicits trills and flat-trills. We addressed this question using eight ovariectomized rats, we investigated whether ovarian hormones augmented these call subtypes in response to CLS. The combined and separate effects of estradiol benzoate (EB) and progesterone (P), and oil vehicle were assessed through comparison of these call subtypes between CLS and inter-CLS interval. We found that CLS with EB + P significantly increased call duration and rate, lowered peak frequency, and widened the bandwidth of trills. Flat-trills showed a similar pattern except for call duration. Call distribution during the CLS and inter-CLS interval suggest that trill and flat-trills may be indicative of both anticipatory and sexual reward.

Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens core of female rats.

Naturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent. Therefore, we examined basal differences in intrinsic NAc excitability of obesity-prone vs. obesity-resistant females and determined how conditioned approach (a measure of cue-triggered motivation), food intake, and motivation for food vary with the cycle in naturally cycling female obesity-prone, obesity-resistant, and outbred Sprague-Dawley rats. Finally, we used ovariectomy followed by hormone treatment to determine the role of ovarian hormones in cue-triggered motivation in selectively-bred and outbred female rats. We found that intrinsic excitability of NAc MSNs and conditioned approach are enhanced in female obesity-prone vs. obesity-resistant rats. These effects were driven by greater MSN excitability and conditioned approach behavior during metestrus/diestrus vs. proestrus/estrus in obesity-prone but not obesity-resistant rats, despite similar regulation of food intake and food motivation by the cycle in these groups. Furthermore, estradiol and progesterone treatment reduced conditioned approach behavior in obesity-prone and outbred Sprague-Dawley females. To our knowledge, these data are the first to demonstrate cycle- and hormone-dependent effects on the motivational response to a food cue, and the only studies to date to determine how individual susceptibility to obesity influences NAc excitability, cue-triggered food-seeking, and differences in the regulation of these neurobehavioral responses by the estrous cycle.

Site-specific effects of aromatase inhibition on the activation of male sexual behavior in male Japanese quail (Coturnix japonica).

Aromatization within the medial preoptic nucleus (POM) is essential for the expression of male copulatory behavior in Japanese quail. However, several nuclei within the social behavior network (SBN) also express aromatase. Whether aromatase in these loci participates in the behavioral activation is not known. Castrated male Japanese quail were implanted with 2 subcutaneous Silastic capsules filled with crystalline testosterone and with bilateral stereotaxic implants filled with the aromatase inhibitor Vorozole targeting the POM, the bed nucleus of the stria terminalis (BST) or the ventromedial nucleus of the hypothalamus (VMN). Control animals were implanted with testosterone and empty bilateral stereotaxic implants. Starting 2 days after the surgery, subjects were tested for the expression of consummatory sexual behavior (CSB) every other day for a total of 10 tests. They were also tested once for appetitive sexual behavior (ASB) as measured by the rhythmic cloacal sphincter movements displayed in response to the visual presentation of a female. CSB was drastically reduced when the Vorozole implants were localized in the POM, but not in the BST nor in the VMN. Birds with implants in the BST took longer to show CSB in the first 6 tests than controls, suggesting a role of the BST in the acquisition of the full copulatory ability. ASB was not significantly affected by aromatase blockade in any region. These data confirm the key role played by the POM in the control of male sexual behavior and suggest a minor role for aromatization in the BST or VMN.

Nicotine Produces a High-Approach, Low-Avoidance Phenotype in Response to Alcohol-Associated Cues in Male Rats.

BACKGROUND: Nicotine and alcohol use are highly comorbid. Modulation of drug-paired extrinsic and intrinsic cues likely plays a role in this interaction, as cues can acquire motivational properties and augment drug seeking. The motivational properties of cues can be measured through Pavlovian conditioning paradigms, in which cues either elicit approach following pairing with the reinforcing properties of alcohol or elicit avoidance following pairing with the aversive consequences of alcohol. The present experiments tested whether nicotine would enhance the incentive properties of an appetitive ethanol (EtOH) cue and diminish the avoidance of an aversive EtOH cue in Pavlovian paradigms. METHODS: In experiment 1, male Long-Evans rats with or without prior chronic intermittent access to EtOH were administered nicotine or saline injections prior to Pavlovian conditioned approach (PavCA) sessions, during which conditioned approach to the cue ("sign-tracking") or the EtOH delivery location ("goal-tracking") was measured. In experiment 2, male Long-Evans rats were administered nicotine or saline injections prior to pairing a flavor cue with increasing doses of EtOH (i.p.) in an adaptation of the conditioned taste avoidance (CTA) paradigm. RESULTS: Results from PavCA indicate that, regardless of EtOH exposure, nicotine enhanced responding elicited by EtOH-paired cues with no effect on a similar cue not explicitly paired with EtOH. Furthermore, nicotine reduced sensitivity to EtOH-induced CTA, as indicated by a rightward shift in the dose-response curve of passively administered EtOH. The ED50 , or the dose of EtOH that produced a 50% reduction in intake relative to baseline, was significantly higher in nicotine-treated rats compared to saline-treated rats. CONCLUSIONS: We conclude that nicotine increases the approach and diminishes the avoidance elicited by Pavlovian cues paired, respectively, with the reinforcing and aversive properties of EtOH consumption in male rats. As such, nicotine may enhance alcoholism liability by engendering an attentional bias toward cues that predict the reinforcing outcomes of drinking.

Nitric oxide and l-arginine regulate feeding in satiated rats.

Nitric Oxide (NO) and its precursor l-arginine were found to inhibit feeding in rats with a low motivation to eat, as they do in Aplysia. In rats that are relatively satiated, treatment with an NO blocker increased feeding, and treatment with an NO donor or with either of 2 doses of l-arginine inhibited feeding. NO and l-arginine modulated several parameters of feeding, such as the total duration of appetitive behaviors, the time spent feeding, the quantity of food eaten and the number of feeding bouts. The inhibitory effect of l-arginine on feeding could not be attributed to changes in locomotion. These data indicate that satiation is partially mediated by increased production of NO. NADPH-Diaphorase histochemical staining, which is specific for tissues actively producing NO, showed significantly greater staining in satiated compared to hungry rats in all 4 hypothalamic nuclei (paraventricular and arcuate nuclei, lateral and ventromedial hypothalamus) that were examined. l-arginine may act as a regulator of feeding by controlling NO production in several hypothalamic nuclei, specifically under condition of a low feeding motivation.

Peripherally injected ghrelin and leptin reduce food hoarding and mass gain in the coal tit (Periparus ater).

In birds little is known about the hormonal signals that communicate nutritional state to the brain and regulate appetitive behaviours. In mammals, the peptide hormones ghrelin and leptin elevate and inhibit consumption and food hoarding, respectively. But in birds, administration of both ghrelin and leptin inhibit food consumption. The role of these hormones in the regulation of food hoarding in avian species has not been examined. To investigate this, we injected wild caught coal tits (Periparus ater) with leptin, high-dose ghrelin, low-dose ghrelin and a saline control in the laboratory. We then measured food hoarding and mass gain, as a proxy of food consumption, every 20 min for 2 h post-injection. Both high-dose ghrelin and leptin injections significantly reduced hoarding and mass gain compared with controls. Our results provide the first evidence that hoarding behaviour can be reduced by both leptin and ghrelin in a wild bird. These findings add to evidence that the hormonal control of food consumption and hoarding in avian species differs from that in mammals. Food hoarding and consumptive behaviours consistently show the same response to peripheral signals of nutritional state, suggesting that the hormonal regulation of food hoarding has evolved from the consumption regulatory system.

Gonadal hormones, but not sex, affect the acquisition and maintenance of a Go/No-Go odor discrimination task in mice.

In mice, olfaction is crucial for identifying social odors (pheromones) that signal the presence of suitable mates. We used a custom-built olfactometer and a thirst-motivated olfactory discrimination Go/No-Go (GNG) task to ask whether discrimination of volatile odors is sexually dimorphic and modulated in mice by adult sex hormones. Males and females gonadectomized prior to training failed to learn even the initial phase of the task, which involved nose poking at a port in one location obtaining water at an adjacent port. Gonadally intact males and females readily learned to seek water when male urine (S+) was present but not when female urine (S-) was present; they also learned the task when non-social odorants (amyl acetate, S+; peppermint, S-) were used. When mice were gonadectomized after training the ability of both sexes to discriminate urinary as well as non-social odors was reduced; however, after receiving testosterone propionate (castrated males) or estradiol benzoate (ovariectomized females), task performance was restored to pre-gonadectomy levels. There were no overall sex differences in performance across gonadal conditions in tests with either set of odors; however, ovariectomized females performed more poorly than castrated males in tests with non-social odors. Our results show that circulating sex hormones enable mice of both sexes to learn a GNG task and that gonadectomy reduces, while hormone replacement restores, their ability to discriminate between odors irrespective of the saliency of the odors used. Thus, gonadal hormones were essential for both learning and maintenance of task performance across sex and odor type.

The effects of felbamate on appetitive and aversive instrumental learning in adult rats.

Antiepileptic medications are the frontline treatment for seizure conditions but are not without cognitive side effects. Previously, our laboratory reported learning deficits in phenytoin-, carbamazepine-, and valproate-treated rats. In the present experiment, the effects of felbamate (FBM) have been compared to water-treated controls (controls) using the same instrumental training tasks employed here. Rats treated with FBM displayed a deficit in acquiring a tone-signaled avoidance response, relative to controls, but this was true only if they had no prior appetitive experience. Terminal avoidance behavior was equivalent to healthy controls. In contrast, the FBM-treated rats showed enhanced acquisition of the avoidance response relative to controls when given the benefit of prior experience in the appetitive condition. Relative to animals treated with phenytoin, carbamazepine, or valproate, FBM-treated rats showed the lowest overall pattern of deficits using these instrumental learning tasks. While FBM treatment has been severely restricted because of rather low risks of serious medical side effects, we suggest that the risks are not substantially higher than those shown to exist for phenytoin, carbamazepine, or valproate. As psychologists, we further suggest that negative cognitive deficits associated with these various drugs, along with their quality-of-life costs, are of relevance in the design of treatment strategies for individuals with seizure disorders.

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.

Layered reward signalling through octopamine and dopamine in Drosophila.

Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the ß-adrenergic-like OCTß2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.