Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens.

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with both in vivo electrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. With ex vivo slice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPN activity in obese mice. Finally, blocking synaptic transmission from D1SPNs decreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNs during food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNs in the development of diet-induced obesity, identifying a novel potential therapeutic target.

Environmental complexity positively impacts affective states of broiler chickens

Affective state can bias an animal’s judgement. Animals in positive affective states can interpret ambiguous cues more positively (“optimistically”) than animals in negative affective states. Thus, judgement bias tests can determine an animal’s affective state through their responses to ambiguous cues. We tested the effects of environmental complexity and stocking density on affective states of broiler chickens through a multimodal judgement bias test. Broilers were trained to approach reinforced locations signaled by one color and not to approach unreinforced locations signaled by a different color. Trained birds were tested for latencies to approach three ambiguous cues of intermediate color and location. Broilers discriminated between cues, with shorter latencies to approach ambiguous cues closest to the reinforced cue than cues closest to the unreinforced cue, validating the use of the test in this context. Broilers housed in high-complexity pens approached ambiguous cues faster than birds in low-complexity pens–an optimistic judgement bias, suggesting the former were in a more positive affective state. Broilers from high-density pens tended to approach all cues faster than birds from low-density pens, possibly because resource competition in their home pen increased food motivation. Overall, our study suggests that environmental complexity improves broilers’ affective states, implying animal welfare benefits of environmental enrichment.

Evaluation of an easy-to-use protocol for assessing behaviors of dogs retiring from commercial breeding kennels

Objective, reliable behavioral tests are needed to refine on-site welfare assessments of dogs housed at commercial breeding (CB) kennels and provide a basis to inform predictions of their behavior when retired from such kennels. This study tested the reliability, construct validity, and applicability of a protocol for the behavioral assessment of dogs from CB kennels that might be useful in comprehensive welfare assessments of this population. A sample of 447 dogs from 26 CB kennels in the Midwestern US were assessed in their pens. Responses to an approach test (performed on three consecutive days) and a behavioral reactivity test (e.g., traffic cone, toys, umbrella) were recorded. Results showed moderate to perfect (Kw = 0.51–1.00) inter-rater reliability between three independent observers. Approach test-retest analysis showed high correlation of approach test scores on days 1, 2 and 3 (r = 0.85, p<0.0001). Exploratory factor analysis extracted four main factors: Food Motivation (F1), Sociability (F2), Boldness (F3) (e.g., response to novel objects), and Responsiveness (F4) (e.g., response to an umbrella opening) confirming the ability of the test to measure behaviors of interest. All factors showed high internal consistency (Cronbach’s alpha 0.81–0.93) further supporting the robustness of the test construct. The demonstrated reliability of this protocol suggests that it may be usefully applied to assessing the behavior of dogs as a component of their welfare assessment in CB kennels. Doing so using even larger sample sizes may yield insights on the effects of housing and management practices on dog welfare while at the kennels, which may also help inform approaches that improve rehoming outcomes for retiring breeding dogs. Practical applications and limitations are outlined.

Failure to Find Altruistic Food Sharing in Rats

Prior research has found that one rat will release a second rat from a restraint in the presence of food, thereby allowing that second rat access to food. Such behavior, clearly beneficial to the second rat and costly to the first, has been interpreted as altruistic. Because clear demonstrations of altruism in rats are rare, such findings deserve a careful look. The present study aimed to replicate this finding, but with more systematic methods to examine whether, and under what conditions, a rat might share food with its cagemate partner. Rats were given repeated choices between high-valued food (sucrose pellets) and 30-s social access to a familiar rat, with the (a) food size (number of food pellets per response), and (b) food motivation (extra-session access to food) varied across conditions. Rats responded consistently for both food and social interaction, but at different levels and with different sensitivity to the food-access manipulations. Food production and consumption was high when food motivation was also high (food restriction) but substantially lower when food motivation was low (unlimited food access). Social release occurred at moderate levels, unaffected by the food-based manipulations. When food was abundant and food motivation low, the rats chose food and social options about equally often, but sharing (food left unconsumed prior to social release) occurred at low levels across sessions and conditions. Even under conditions of low food motivation, sharing occurred on only 1% of the sharing opportunities. The results are therefore inconsistent with claims in the literature that rats are altruistically motivated to share food with other rats.

Relationship Between Oxytocin Levels and Brain Volume in Anorexia Nervosa Compared to Healthy Controls

Background: A disruption in food motivation pathways has been described in females with anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low weight. We have shown that in AN and healthy controls (HC), levels of oxytocin (OXT), a hormone involved in lactation, social behavior and weight regulation, decrease after a meal. In HC, we identified a relationship between postprandial change in OXT and subjective appetite, yet this association was absent in females with AN, suggesting a disconnect between OXT and appetite regulation in AN. Prior studies have shown that gray matter volume of the amygdala and hippocampus, areas rich in OXT receptors, correlate with OXT levels in HC. Furthermore, these regions play a central role in food reward and decreased volume has been reported in AN. We hypothesized that the relationship between postprandial change in OXT and amygdala and hippocampal gray matter volume would differ between AN and HC. Methods: We performed a cross-sectional study of 51 females (23 restrictive AN; 28 HC). We drew blood for OXT levels fasting and 60 min after a standard meal and performed T1-weighted MRI scans of the brain in the fasted state. MRI data was quality controlled and processed with FreeSurfer. Average gray matter brain volumes were extracted from the bilateral amygdala and hippocampus for each subject. Linear regression models were used to determine differences between AN and HC of postprandial percent change in OXT on amygdala and hippocampus gray matter volume. Results: Median [IQR] age was higher in females with AN (20.6 years [19.3, 21.5]) than HC (18.8 years [IQR 17.6, 20.3], p=0.02), and percentage of ideal body weight was lower in AN (75.5%) than HC (97.4%, p&lt;0.01). Right hippocampus volume, adjusted for age and total intracranial volume, was significantly lower in AN (estimated difference -188 dm3 [95%-CI -360, -17], p=0.04). Percent change in OXT was not different (p=0.5) but there was a trend for a positive interaction effect (p=0.08) for AN and percent change in OXT on right hippocampus volume. Posthoc exploratory analysis indicated a positive correlation in AN (R2=0.41, p=0.02) and no correlation in HC (R2=0.17,p=0.4) between percent change in OXT and right hippocampus volume. There was no significant between group difference in volume nor postprandial change in OXT for the bilateral amygdala or left hippocampus between groups. Discussion: Our results indicate smaller right hippocampus volume and a trend towards a positive association with postprandial change in OXT in AN compared to HC. Future studies will be important to better define the relationships between OXT secretion and food motivation brain regions and the impact on eating behavior in AN.

Absence of Sex Differences Identified in Food Motivation Pathways in Youth with Avoidant/Restrictive Food Intake Disorder (ARFID)

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a recent diagnosis incorporated into the DSM-5 to provide diagnostic specificity to individuals who may have avoidant/restrictive eating behavior unrelated to body image/weight concerns and display three core profiles: insufficient intake/low interest in feeding, fear of aversive consequences related to food intake (e.g., choking) and avoidance based on sensory characteristics of food. Various studies have shown a higher preponderance of male patients in ARFID compared to other eating disorder groups. To elucidate potential sex differences in the neurobiology of ARFID, we examined food motivation pathways by assessing levels of key appetite regulating hormones, anorexigenic peptide YY (PYY) and orexigenic ghrelin, and fMRI activation of relevant brain circuitry in females compared to males with ARFID. Based on prior fMRI studies in healthy controls, we hypothesized that in a fasted state, females (vs. males) would demonstrate greater blood-oxygen-level-dependent (BOLD) activation in response to high-calorie food (vs. non-food) images in the orbitofrontal cortex (OFC) and the right lateral prefrontal cortex (LPFC), while males (vs. females) would demonstrate greater activation in the right hippocampus. Methods: Seventy-five adolescents and young adults with ARFID and sub-threshold ARFID (43 female) were studied after a 10-hour overnight fast. PYY and ghrelin levels were assessed in a subset of 62 individuals (31 female). All participants completed fMRI imaging in a 3T scanner while viewing images of foods, non-food items, and fixation stimuli. Functional MRI data were analyzed using SPM12. A priori regions of interest included the right lateral prefrontal cortex (LPFC), right hippocampus and orbitofrontal cortex (OFC). Secondary exploratory whole-brain analysis was also performed. Statistical significance is reported at the p&lt;0.05 level. Results: Females and males did not differ in age ((mean±SD): 16.1±3.7 years) or BMI (19.9±5.4 kg/m2). There were no statistically significant differences between females and males in PYY (p=0.10) or ghrelin (p=0.47) levels. Furthermore, analysis of fMRI data yielded no significant differences between females and males with ARFID in a priori regions of interest (OFC: p(FWE-corr)&gt;0.50; R LPFC: no suprathreshold clusters, or R hippocampus: p(FWE-corr)=0.25 and 0.33) or in the secondary whole-brain analysis (cluster p(FWE-corr)=0.304). Conclusion: This is the first study to investigate sex differences in the neurobiology of ARFID, an important line of research to advance treatment approaches. We found no sex-specific neurobiological differences in adolescents and young adults with ARFID. Future studies with larger sample sizes are needed to further investigate potential sex differences across the different ARFID profiles.

An open-source device for measuring food intake and operant behavior in rodent home-cages

Feeding is critical for survival and disruption in the mechanisms that govern food intake underlie disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: The Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs.