Food-rewarded Task Research Articles

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

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

Behaviourally-mediated learning ability in an invasive marine fish

Invasive species can have profound impacts in non-native environments, the mechanisms behind which are often unclear. Learning and memory are notably two traits that may facilitate their impact. Behavioural traits can subsequently mediate learning ability in invasive species, the interaction between which may provide means by which to both better understand and manage invaders. We evaluated this relationship in lionfish (Pterois volitans), a species introduced to and invasive in the western Atlantic Ocean. We trained lionfish in a food reward task and assessed the degree to which behavioural traits and navigation strategy influenced their performance. We then evaluated memory retention by subjecting fish to training breaks of 5 to 42 days. Lionfish exhibited high inter-individual variability in learning. Half of the lionfish tested learned to navigate the maze, whose performance was strongly mediated by behaviour. Learning ability was positively correlated with boldness, exploratory tendency, and speed of task completion, but irrespective of spatial navigation strategy. However, fast exploratory fish trained in the complex navigation strategy had difficulty adapting to changing environmental conditions, indicative of a speed-accuracy trade-off. Lionfish were able to remember the location of the food reward for up to 6 weeks. Behavioural-mediated learning may help explain and understand the high impact of lionfish and other non-indigenous species in their invaded range and may elucidate spatiotemporal context-dependencies in their ecological impact.

Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults: A randomised crossover trial

BackgroundFew studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. ObjectiveTo investigate the effect of hydration status on multiple facets of appetite. DesignAfter 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. ResultsHYPO induced -1.9 ± 1.2% body mass change, compared to -0.2 ± 0.6% , with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27–32 mm across all time points) and lower fasted desire for salt (−23, 95% CI −10, −35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg mL−1, EUHY 188 ± 71 pg mL−1; p = 0.736) were similar by hydration status. ConclusionsAn acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.

Chronic corticosterone treatment enhances extinction-induced depression in aged rats

Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3–4months) and aged (18months) male rats were treated with CORT via drinking water for 3weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression.

Neuronal Food Reward Activity in Patients With Type 2 Diabetes With Improved Glycemic Control After Bariatric Surgery

Obesity and type 2 diabetes mellitus (T2DM) are associated with altered food-related neuronal functions. Besides weight loss, substantial improvement of glucose metabolism in patients with T2DM can be achieved by bariatric surgery. We aimed to target the neuronal and behavioral correlates of improved glycemic control after bariatric surgery. Two patient groups with T2DM were recruited. The treatment group (n = 12) consisted of patients who had undergone Roux-en-Y gastric bypass (RYGB) surgery, and a control group consisted of patients who did not undergo surgery (n = 12). The groups were matched for age and current BMI. HbA1c was matched by using the presurgical HbA1c of the RYGB group and the current HbA1c of the nonsurgical group. Neuronal activation during a food reward task was measured using functional MRI (fMRI). Behavioral data were assessed through questionnaires. RYGB improved HbA1c from 7.07 ± 0.50 to 5.70 ± 0.16% (P < 0.05) and BMI from 52.21 ± 1.90 to 35.71 ± 0.84 kg/m(2) (P < 0.001). Behavioral results showed lower wanting and liking scores as well as lower eating behavior-related pathologies for the patients after RYGB than for similar obese subjects without surgery but with impaired glycemic control. The fMRI analysis showed higher activation for the nonsurgical group in areas associated with inhibition and reward as well as in the precuneus, a major connectivity hub in the brain. By contrast, patients after RYGB showed higher activation in the visual, motor, cognitive control, memory, and gustatory regions. In obese patients with diabetes, RYGB normalizes glycemic control and leads to food reward-related brain activation patterns that are different from those of obese patients with less-well-controlled T2DM and without bariatric surgery. The differences in food reward processing might be one factor in determining the outcome of bariatric surgery in patients with T2DM.

Associations between sleep parameters and food reward.

This study examined the effects of acute, isocaloric aerobic and resistance exercise on different sleep parameters, and whether changes in these sleep parameters between sessions were related to next morning food reward. Fourteen men and women (age: 21.9 ± 2.7 years; body mass index: 22.7 ± 1.9 kg m(-) ²) participated in three randomized crossover sessions: aerobic exercise; resistance exercise; and sedentary control. Target exercise energy expenditure was matched at 4 kcal kg(-1) of body weight, and performed at 70% of VO2peak or 70% of 1 repetition-maximal. Sleep was measured (accelerometry) for 22 h following each session. The 'wanting' for visual food cues (validated computer task) was assessed the next morning. There were no differences in sleep parameters and food 'wanting' between conditions. Decreases in sleep duration and earlier wake-times were significantly associated with increased food 'wanting' between sessions (P = 0.001). However, these associations were no longer significant after controlling for elapsed time between wake-time and the food reward task. These findings suggest that shorter sleep durations and earlier wake-times are associated with increased food reward, but these associations are driven by elapsed time between awakening and completion of the food reward task.

Noradrenergic but not cholinergic modulation of olfactory bulb during processing of near threshold concentration stimuli.

Neuromodulatory systems such as noradrenaline (NE), acetylcholine (ACh), and serotonin (5HT) serve important functions in sensory perception. We use the olfactory bulb (OB) as a model system to study the roles of individual neuromodulators in sensory perception. Using a spontaneous, nonreward motivated detection task, as well as a reward-motivated task, we show that rats can easily respond to odorants at very low concentrations when motivated to do so in a food-rewarded task, despite not showing spontaneous responses to these low concentration odorants. Using the same tasks paired with local bulbar infusions of noradrenergic and cholinergic drugs, we then show that rats engage their noradrenergic, but not their cholinergic system, to better respond to near threshold odorants. These results suggest that while cholinergic modulation of OB function is mostly important for odor decorrelation and discrimination, noradrenergic modulation is important for signal-to-noise modulation.

Sucrose self-administration and CNS activation in the rat.

We have previously reported that administration of insulin into the arcuate nucleus of the hypothalamus decreases motivation for sucrose, assessed by a self-administration task, in rats. Because the pattern of central nervous system (CNS) activation in association with sucrose self-administration has not been evaluated, in the present study, we measured expression of c-Fos as an index of neuronal activation. We trained rats to bar-press for sucrose, according to a fixed-ratio (FR) or progressive-ratio (PR) schedule and mapped expression of c-Fos immunoreactivity in the CNS, compared with c-Fos expression in handled controls. We observed a unique expression of c-Fos in the medial hypothalamus (the arcuate, paraventricular, retrochiasmatic, dorsomedial, and ventromedial nuclei) in association with the onset of PR performance, and expression of c-Fos in the lateral hypothalamus and the bed nucleus of stria terminalis in association with the onset of FR performance. c-Fos expression was increased in the nucleus accumbens of both FR and PR rats. Our study emphasizes the importance of both hypothalamic energy homeostasis circuitry and limbic circuitry in the performance of a food reward task. Given the role of the medial hypothalamus in regulation of energy balance, our study suggests that this circuitry may contribute to reward regulation within the larger context of energy homeostasis.

Lead and spatial vs. cued open field performance

Male Fischer 344 rats received chronic exposure to either water containing 250 ppm lead or tap water. On the first day of the study, rats were allowed to habituate to a 1-m 2 open field arena with a rectilinear grid pattern of food wells on the floor for a 2-min session. On the following 7 days, half the rats were trained (four trials per day, 2–4-min intertrial interval) to find a food location based on extra-maze spatial cues and the other half were trained to find a food location based on a discrete intra-maze cue placed over the baited food well. While lead did not appear to significantly affect motor activity during the habituation phase, lead-exposed spatially trained rats exhibited superior acquisition and performance of the food-rewarded task compared to their controls and their cue-trained lead-exposed and counterparts. Furthermore, by the last day of training, Day 7, lead significantly reduced the relative amount of time spent on the periphery of the maze in spatially and cued-trained rats.

Tolerance to the discriminative stimulus effects of ethanol

These experiments tested (1) the specificity of the discriminative stimulus produced by ethanol (EtOH), (2) the ability of Ro 15-4513 to block the EtOH stimulus, and (3) whether tolerance would develop to the discriminative effects of EtOH following high-dose EtOH administration. Rats were trained to use EtOH, 1 g/kg, i.p., as a discriminative stimulus in a two-choice, food-reward task. Following establishment of stimulus control, EtOH and pentobarbital substituted for EtOH in a dose-related manner; in contrast, pentylene-tetrazole and cocaine produced responding on the vehicle lever. Ro 15-4513, a partial inverse agonist at benzodiazepine receptors, failed to block the EtOH stimulus. Following these experiments, subjects were withheld from training and given EtOH in a nutritionally complete liquid diet, in two feedings per day for 6 days. Subjects consumed approximately 10 g of EtOH per day from this diet. On days 4 to 6 of this regimen, 12-h after a previous EtOH feeding, subjects were retested with EtOH. After recovery from this procedure and re-establishment of baseline performance, subjects were again given the high-dose EtOH treatment and tested for pentobarbital substitution. High-dose EtOH produced tolerance to EtOH and some degree of cross-tolerance to pentobarbital. These results are consistent with the hypothesis that chronic EtOH administration produces tolerance to the stimulus effects of EtOH.

Effects of the training dose on generalization of morphine stimulus to clonidine

The relationship between the stimulus properties of morphine and clonidine was tested in rats trained to discriminate morphine sulfate (4, 2 or 1 mg/kg) from saline in a two-lever food-rewarded task. The response trained in the low dose group generalized only to higher doses of clonidine (0.125 to 0.5 mg/kg) whereas the response trained with the high dose of morphine generalized only to higher doses of clonidine (0.625 to 1.0 mg/kg). Naloxone blocked the generalization in the low dose group but only partially blocked it in the high dose group. Yohimbine blocked the generalization to clonidine in the high morphine dose group and reversed the response rate suppressant effect of clonidine in all groups.

The effect of bilateral ventral noradrenaline bundle lesions on lever pressing for food in rats.

Food reward has been associated with activation of noradrenergic mechanisms in the brain. Using rats trained to press a lever for food reward, we have investigated the effects of 6-hydroxydopamine lesions, which severly depleted hypothalamic noradrenaline, on the willingness of the rats to press the lever for food reward. We found that performance in the food-rewarded task was significantly impaired following such lesions, and that this was especially marked when the task was made more difficult. From our results we suggest that ventral noradrenaline bundle lesions can decrease the rewarding nature of food, thus making the animals less willing to work for food reward.