Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast.

The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala's involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.

Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food Consumption.

Decades of research have shown that the NAc is a critical region influencing addiction, mood, and food consumption through its effects on reinforcement learning, motivation, and hedonic experience. Pharmacological studies have demonstrated that inhibition of the NAc shell induces voracious feeding, leading to the hypothesis that the inhibitory projections that emerge from the NAc normally act to restrict feeding. While much of this work has focused on projections to the lateral hypothalamus, the role of NAc projections to the VTA in the control food intake has been largely unexplored. Using a retrograde viral labeling technique and real-time monitoring of neural activity with fiber photometry, we find that medial NAc shell projections to the VTA (mNAc→VTA) are inhibited during food-seeking and food consumption in male mice. We also demonstrate that this circuit bidirectionally controls feeding: optogenetic activation of NAc projections to the VTA inhibits food-seeking and food intake (in both sexes), while optogenetic inhibition of this circuit potentiates food-seeking behavior. Additionally, we show that activity of the NAc to VTA pathway is necessary for adaptive inhibition of food intake in response to external cues. These data provide new insight into NAc control over feeding in mice, and contribute to an emerging literature elucidating the role of inhibitory midbrain feedback within the mesolimbic circuit.SIGNIFICANCE STATEMENT The medial NAc has long been known to control consummatory behavior, with particular focus on accumbens projections to the lateral hypothalamus. Conversely, NAc projections to the VTA have mainly been studied in the context of drug reward. We show that NAc projections to the VTA bidirectionally control food intake, consistent with a permissive role in feeding. Additionally, we show that this circuit is normally inactivated during consumption and food-seeking. Together, these findings elucidate how mesolimbic circuits control food consumption.

Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man.

Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

Habitual Ethanol Seeking and Licking Microstructure of Enhanced Ethanol Self-Administration in Ethanol-Dependent Mice.

BACKGROUND: A significant component of ethanol (EtOH) dependence is the disruption to decision-making processes. Prior work has shown EtOH dependence biases habitual seeking of EtOH and disrupts neural mechanisms supporting decision-making. This has contributed to the hypothesis that habitual EtOH seeking in EtOH dependence may promote excessive habitual or compulsive EtOH consumption. However, decision-making and behavioral processes underlying seeking and consummatory behaviors differ. Here, we examine the microstructure of EtOH consummatory behavior in the context of habitual EtOH seeking. METHODS: Following home cage pre-exposure to EtOH, C57Bl/6J mice underwent 4 rounds of chronic intermittent EtOH (CIE) or air exposure. Following acute withdrawal, mice began training for operant self-administration of 15% EtOH. Training consisted of 16-hour sessions in which mice were trained in a random ratio (RR) schedule of reinforcement for 30-second access to the EtOH sipper. To test for CIE-induced changes in action control, we used sensory-specific satiation and assessed the effect of outcome devaluation on EtOH seeking. Importantly, the use of a lickometer during operant training allowed us to measure the microstructure of lick behavior. RESULTS: Prior induction of EtOH dependence led to increased EtOH seeking, consumption, and an insensitivity to outcome devaluation, the latter indicative of habitual EtOH seeking. We also found altered consummatory lick patterns in CIE-exposed mice compared to Air controls. While CIE mice had significantly more licks in a burst and a longer burst duration, there were no differences in the total number of bursts compared to Air controls. Furthermore, these EtOH consummatory behaviors correlated with blood EtOH concentrations (BECs), while EtOH-seeking responses did not. CONCLUSIONS: Our results confirm that EtOH dependence can produce habitual EtOH seeking and suggests the increased EtOH consummatory behaviors following EtOH dependence are separable from decision-making processes controlling EtOH seeking.

Commensal microbiota modulates larval foraging behaviour, development rate and pupal production in Bactrocera tryoni.

BACKROUND: Commensal microbes can promote survival and growth of developing insects, and have important fitness implications in adulthood. Insect larvae can acquire commensal microbes through two main routes: by vertical acquisition from maternal deposition of microbes on the eggshells and by horizontal acquisition from the environment where the larvae develop. To date, however, little is known about how microbes acquired through these different routes interact to shape insect development. In the present study, we investigated how vertically and horizontally acquired microbiota influence larval foraging behaviour, development time to pupation and pupal production in the Queensland fruit fly ('Qfly'), Bactrocera tryoni. RESULTS: Both vertically and horizontally acquired microbiota were required to maximise pupal production in Qfly. Moreover, larvae exposed to both vertically and horizontally acquired microbiota pupated sooner than those exposed to no microbiota, or only to horizontally acquired microbiota. Larval foraging behaviour was also influenced by both vertically and horizontally acquired microbiota. Larvae from treatments exposed to neither vertically nor horizontally acquired microbiota spent more time overall on foraging patches than did larvae of other treatments, and most notably had greater preference for diets with extreme protein or sugar compositions. CONCLUSION: The integrity of the microbiota early in life is important for larval foraging behaviour, development time to pupation, and pupal production in Qflies. These findings highlight the complexity of microbial relations in this species, and provide insights to the importance of exposure to microbial communities during laboratory- or mass-rearing of tephritid fruit flies.

Consumption of Euterpe edulis fruit by wildlife: implications for conservation and management of the Southern Brazilian Atlantic Forest.

This study aimed to measure the wildlife consumption of Euterpe edulis fruit and use this data to discuss management possibilities. To estimate infructescence fruit volume consumed, collectors were installed in fruit-bearing palms. To characterize consumption from the ground, samples were placed next to fruiting palms. To identify wildlife and their activities, camera traps were installed in infructescences and on the ground. The results suggested that there was a small fruit surplus (1.8 %), and this finding indicated the possibility of a harvest to reduce food for the wildlife. However, recurrent variations in the annual fruit production (21.4 %) were also noted, and suggested that wildlife could tolerate some fruit harvesting. Thus, a harvest could be restricted to fruit volume that exceeds the annual average (94 kg/ha/year). Turdus flavipes, a migratory bird, was the most active species in the dispersal of seeds; this finding indicates the need for broader conservation strategies. Wildlife composition also changed along with the fruiting, and this alteration suggests that dependence on the fruit is variable among different species. Seed germination and seedling mortality were high, results that indicate that local conditions may have a predominant effect on seed volume in natural regeneration density.

A Review of "Polychaeta" Chemicals and their Possible Ecological Role.

Despite the many publications concerning the isolation of substances and the many reviews of marine natural products, some groups of organisms remain poorly studied, including "Polychaeta". In response, this review covers articles published through December 2016 that address marine natural products produced from polychaetes, with a focus on antipredatory strategies, competitors, fouling, and pathogens. A total of 121 compounds were isolated from 1934 to 2016, which includes halogenated aromatics, proteins, amino acids and Lumazine derivatives most notably-with a defensive function were found in the literature, most frequently in the families Sabellidae, Terebellidae, Glyceridae, and Nereididae. The period of highest discovery of natural products in defensive actions for the group was the 2000s. Polychaetes were addressed in 26 revisions of the total 51 articles analyzed and are less reported than other marine invertebrates such as sponges, cnidarians, mollusks, and tunicates. In sum, the present review provides a basis for future research on the marine chemical ecology of polychaetes.

Consummatory succesive positive contrast produced by the downshift of an aversive solution in infant rats.

Subjects trained in successive positive contrast are usually given an appetitive stimulus of relatively low quality during a pre-shift, followed by exposure to a significantly greater quality of the same stimulus. Enhanced responsiveness to the high-quality stimulus during the post-shift phase, compared to a control group that receives the superior reward in both phases, is taken as an index of successive positive contrast. Successive positive contrast reports are rare, probably due to performance limitations inherent to the experimental protocols available. We exposed infant rats (14 days old at the start of training) to .1% or .01% quinine during 4, 10 min, trials (pre-shift phase). All animals were then given two trials of exposure to .01% quinine (post-shift phase). During the pre-shift the level of intake was greater in pups stimulated with the relatively less aversive .01% quinine solution. These animals also exhibited, compared to those stimulated with .1% quinine, lower emission of the aversive response paw treading. During the post-shift phase, the group that had been exposed to .1% quinine exhibited significantly greater intake of .01% quinine, along with a reduction in the emission of paw treading and an enhancement in paw licking, an ingestive, appetitive response. Altogether, the evidence is suggestive of the emergence of consummatory successive positive contrast during the second week of life of the rat. To our knowledge, this is the first evidence of positive contrast using an aversive solution.

Role of bed nucleus of the stria terminalis corticotrophin-releasing factor receptors in frustration stress-induced binge-like palatable food consumption in female rats with a history of food restriction.

We developed recently a binge-eating model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after 15 min exposure to the sight of the palatable food. This "frustration stress" manipulation also activates the hypothalamic-pituitary-adrenal stress axis. Here, we determined the role of the stress neurohormone corticotropin-releasing factor (CRF) in stress-induced binge eating in our model. We also assessed the role of CRF receptors in the bed nucleus of the stria terminalis (BNST), a brain region implicated in stress responses and stress-induced drug seeking, in stress-induced binge eating. We used four groups that were first exposed or not exposed to repeated intermittent cycles of regular chow food restriction during which they were also given intermittent access to high-caloric palatable food. On the test day, we either exposed or did not expose the rats to the sight of the palatable food for 15 min (frustration stress) before assessing food consumption for 2 h. We found that systemic injections of the CRF1 receptor antagonist R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7 dipropylamino pyrazolo[1,5-a]pyrimidine) (10-20 mg/kg) and BNST (25-50 ng/side) or ventricular (1000 ng) injections of the nonselective CRF receptor antagonist D-Phe-CRF(12-41) decreased frustration stress-induced binge eating in rats with a history of food restriction. Frustration stress also increased Fos (a neuronal activity marker) expression in ventral and dorsal BNST. Results demonstrate a critical role of CRF receptors in BNST in stress-induced binge eating in our rat model. CRF1 receptor antagonists may represent a novel pharmacological treatment for bingeing-related eating disorders.

Differential contribution of hippocampal circuits to appetitive and consummatory behaviors during operant conditioning of behaving mice.

Operant conditioning is a type of associative learning involving different and complex sensorimotor and cognitive processes. Because the hippocampus has been related to some motor and cognitive functions involved in this type of learning (such as object recognition, spatial orientation, and associative learning tasks), we decided to study in behaving mice the putative changes in strength taking place at the hippocampal CA3-CA1 synapses during the acquisition and performance of an operant conditioning task. Mice were chronically implanted with stimulating electrodes in the Schaffer collaterals and with recording electrodes in the hippocampal CA1 area and trained to an operant task using a fixed-ratio (1:1) schedule. We recorded the field EPSPs (fEPSPs) evoked at the CA3-CA1 synapse during the performance of appetitive (going to the lever, lever press) and consummatory (going to the feeder, eating) behaviors. In addition, we recorded the local field potential activity of the CA1 area during similar behavioral displays. fEPSPs evoked at the CA3-CA1 synapse presented larger amplitudes for appetitive than for consummatory behaviors. This differential change in synaptic strength took place in relation to the learning process, depending mainly on the moment in which mice reached the selected criterion. Thus, selective changes in CA3-CA1 synaptic strength were dependent on both the behavior display and the learning stage. In addition, significant changes in theta band power peaks and their corresponding discrete frequencies were noticed during these behaviors across the sequence of events characterizing this type of associative learning but not during the acquisition process.

Proactive interference of open field on consummatory successive negative contrast.

Reactivity to a reward is affected by prior experience with the different reinforcer values of that reward, a phenomenon known as incentive relativity, which can be studied using the consummatory succesive negative contrast (cSNC) paradigm, in which the performance of animals that receive a 4 % sucrose solution after trials on which they were exposed to 32 % sucrose is compared with that of subjects that always receive the 4 % sucrose solution. The exploration of a novel open field can enhance or block the acquisition of associative and nonassociative memories. The effect of open field on cSNC has not yet been explored. The main result of the present study was that open-field exposure significantly modified the expression of cSNC. Exposure to an open field 1 h but not immediately before the downshift interfered with the expression of cSNC. These animals drank more of the downshifted reward than did controls that were not exposed to the apparatus, and this behavior persisted for up to three recovery trials. This phenomenon was observed even when the animals were given a more protracted preshift phase and when the discrepancy between the preshift and shift incentive values of sucrose were increased. An open field also interfered with incentive downshift when open-field exposure occurred 6 h before the downshift, and repeated exposure to the apparatus did not deteriorate this effect. The present study adds to a growing body of literature that indicates that open-field exploration can interfere with memory formation.

Speed and accuracy of taste identification and palatability: impact of learning, reward expectancy, and consummatory licking.

Despite decades of study, it remains a matter of controversy as to whether in rats taste identification is a rapid process that occurs in about 250-600 ms (one to three licks) or a slow process that evolves over seconds. To address this issue, we trained rats to perform a taste-cued two-response discrimination task (2-RDT). It was found that, after learning, regardless of intensity, the delivery of 10 µl of a tastant (e.g., NaCl or monopotassium glutamate, MPG) was sufficient to identify its taste with maximal accuracy within 400 ms. However, despite overtraining, rats rarely stopped licking in one lick. Thus, a one-drop lick reaction task was developed in which subjects had to rapidly stop licking after release of a stop signal (tastants including water) to obtain rewards. The faster they stopped licking, the greater the reward. Rats did not stop licking after receiving either hedonically positive or negative stop signals, and thus failed to maximize rewards even when reinforced with even larger rewards. In fact, the higher the sucrose concentration given as a stop signal, the greater the number of consummatory licks elicited. However, with a stop signal of 2 mM quinine HCl, they stopped licking in ~370 ms, a time faster than that for sucrose or water, thus showing that in this rapid period, quinine HCl evoked an unpalatable response. Indeed, only when rats licked an empty sipper tube would they usually elicit a single lick to obtain a reward (operant licking). In summary, these data indicate that within 400 ms, taste identification and palatability, must either occur simultaneously or with marked overlap.

An operant ethanol self-administration paradigm that discriminates between appetitive and consummatory behaviors reveals distinct behavioral phenotypes in commonly used rat strains.

Alcohol use disorder (AUD) constitutes a major burden to global health. Recently, the translational success of animal models of AUD has come under increased scrutiny. Efforts to refine models to gain a more precise understanding of the neurobiology of addiction are warranted. Appetitive responding for ethanol (seeking) and its consumption (taking) are governed by distinct neurobiological mechanisms. However, consumption is often inferred from appetitive responding in operant ethanol self-administration paradigms, preventing identification of distinct experimental effects on seeking and taking. In the present study, male Long-Evans, Wistar, and Sprague-Dawley rats were trained to lever press for ethanol using a lickometer-equipped system that precisely measures both appetitive and consummatory behavior. Three distinct operant phenotypes emerged during training: 1) Drinkers, who lever press and consume ethanol; 2) Responders, who lever press but consume little to no ethanol; and 3) Non-responders, who do not lever press. While the prevalence of each phenotype differed across strains, appetitive and consummatory behavior was similar across strains within each phenotype. Appetitive and consummatory behaviors were significantly correlated in Drinkers, but not Responders. Analysis of drinking microstructure showed that greater consumption in Drinkers relative to Responders is due to increased incentive for ethanol rather than increased palatability. Importantly, withdrawal from chronic ethanol exposure resulted in a significant increase in appetitive responding in both Drinkers and Responders, but only Drinkers exhibited a concomitant increase in ethanol consumption. Together, these data reveal important strain differences in appetitive and consummatory responding for ethanol and uncover the presence of distinct operant phenotypes.

Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice.

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

Behavioral evidence for the significance of serotoninergic (5-HT) receptors in cocaine addiction.

Cocaine addiction has somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Presently, there is no medication approved for the treatment of cocaine addiction. In recent years, data from the literature (pre-clinical studies and clinical trials) have provided several lines of evidence that serotonin (5-HT) and 5-HT receptors play a modulatory role in the mechanisms of action of cocaine. Here we review the contribution of 5-HT receptor subtypes to cocaine sensitization, discrimination, conditioned place preference, self-administration, reinstatement of seeking behavior and withdrawal symptoms in laboratory animals. Additionally, the consequences of chronic cocaine exposure on particular 5-HT receptor-assigned functions in pre-clinical studies are presented.

Six clarifications for behaviour systems.

The precursors of contemporary behaviour systems theory were hotly debated, and yet a similar critical fervour has not followed the second generation of behaviour systems research. I raise six items of potential or extant misunderstanding concerning behaviour systems perspectives, and attempt to set straight some of the assumptions and what motivated them, with attention to historical and theoretical context. The six challenges in focus are: 1) variety of conceptualisation of consummation; 2) potential misapprehensions about the role of general search; 3) ambiguity of predictions concerning response form; 4) ambiguity concerning what aspects are modelled as hierarchical; 5) assumptions of directedness; and 6) the relevance of spontaneous activity. For each of these six issues, some clarification is offered.

High-fat food biases hypothalamic and mesolimbic expression of consummatory drives.

Maintaining healthy body weight is increasingly difficult in our obesogenic environment. Dieting efforts are often overpowered by the internal drive to consume energy-dense foods. Although the selection of calorically rich substrates over healthier options is identifiable across species, the mechanisms behind this choice remain poorly understood. Using a passive devaluation paradigm, we found that exposure to high-fat diet (HFD) suppresses the intake of nutritionally balanced standard chow diet (SD) irrespective of age, sex, body mass accrual and functional leptin or melanocortin-4 receptor signaling. Longitudinal recordings revealed that this SD devaluation and subsequent shift toward HFD consumption is encoded at the level of hypothalamic agouti-related peptide neurons and mesolimbic dopamine signaling. Prior HFD consumption vastly diminished the capacity of SD to alleviate the negative valence associated with hunger and the rewarding properties of food discovery even after periods of HFD abstinence. These data reveal a neural basis behind the hardships of dieting.

Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice.

Growth hormone secretagogue receptor (GHSR), the receptor for ghrelin, is expressed in key brain nuclei that regulate food intake. The dopamine (DA) pathways have long been recognized to play key roles mediating GHSR effects on feeding behaviors. Here, we aimed to determine the role of GHSR in DA neurons controlling appetitive and consummatory behaviors towards high fat (HF) diet. For this purpose, we crossed reactivable GHSR-deficient mice with DA transporter (DAT)-Cre mice, which express Cre recombinase under the DAT promoter that is active exclusively in DA neurons, to generate mice with GHSR expression limited to DA neurons (DAT-GHSR mice). We found that DAT-GHSR mice show an increase of c-Fos levels in brain areas containing DA neurons after ghrelin treatment, in a similar fashion as seen in wild-type mice; however, they did not increase food intake or locomotor activity in response to systemically- or centrally-administered ghrelin. In addition, we found that satiated DAT-GHSR mice displayed both anticipatory activity to scheduled HF diet exposure and HF intake in a binge-like eating protocol similar to those in wild-type mice, whereas GHSR-deficient mice displayed impaired responses. We conclude that GHSR expression in DA neurons is sufficient to both mediate increased anticipatory activity to a scheduled HF diet exposure and fully orchestrate binge-like HF intake, but it is insufficient to restore the acute orexigenic or locomotor effects of ghrelin treatment. Thus, GHSR in DA neurons affects appetitive and consummatory behaviors towards HF diet that take place in the absence of caloric needs.

Tail pinch induces eating in sated rats which appears to depend on nigrostriatal dopamine.

Mild tail pinch reliably and rapidly induced eating, gnawing, or licking behavior in all animals tested. Eating was by far the predominant response. Pharmacological analysis of the involvement of the brain catecholamines in tail-pinch behavior suggests that it is critically dependent on the nigrostriatal dopamine system.

Consumers that are not 'ideal' or 'free' can still approach the ideal free distribution using simple patch-leaving rules.

1. The ideal free distribution (IFD) has been widely used to determine whether consumers distribute themselves optimally. However, this theory is based on three assumptions that are clearly violated in many systems. The theory assumes that all individuals know the quality of each available site, are equally free to move between all sites, and have equal competitive abilities. 2. I examine the utility of this theory to predict the distribution of the invasive European green crab Carcinus maenas, a species that likely violates all of these assumptions. I demonstrate three main findings. 3. First, understanding how density-dependent interference and size alter individual foraging behaviour is important for understanding the density and biomass distribution of C. maenas in invaded habitats. 4. Second, once behavioural mechanisms of crab foraging are accurately included in the model, the IFD does a good job of predicting the distribution of C. maenas, even though C. maenas violates the theory's fundamental assumptions. 5. Third, C. maenas' distribution can be obtained using simple decision rules and reasonable movement patterns.