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McCutcheon, J. E.

Publications and source records attributed to McCutcheon, J. E..

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Protein restriction amplifies nucleus accumbens dopamine responses to protein-containing food during operant feeding in male mice

Animals defend protein intake strongly, yet how protein status shapes moment-to-moment reward signalling in mesolimbic circuits remains unclear. Here, we examined how dietary protein restriction shapes nucleus accumbens (NAc) core dopamine signalling during operant feeding in the home-cage. C57BL/6 mice expressing the GRABDA sensor in NAc core performed 1 h fixed-ratio 1 (FR1) and progressive ratio (ProgRatio) sessions to earn grain or sucrose pellets across three dietary phases; an initial non-restricted phase (NR1), a protein-restricted phase (PR), and a return to the non-restricted diet (NR2). Home-cage food intake remained stable across phases, whereas bodyweight gain was markedly reduced during PR and partially recovered in NR2. Behaviourally, operant responding increased during PR under both FR1 and ProgRatio schedules, with the most robust enhancement observed for grain pellets. Fibre photometry revealed a more selective neural effect. During FR1, pellet delivery evoked a larger NAc dopamine response for grain than for sucrose specifically during PR, whereas no pellet-type difference was detected during NR1 or NR2. By contrast, under progressive ratio, dopamine responses at pellet delivery and pellet retrieval did not differ between pellet types in any dietary phase. Together, these findings show that protein restriction does not globally amplify reward-related behaviour or dopamine signalling, but instead selectively biases NAc dopamine encoding in a manner that depends on nutritional status of the animal, nutrient context, and task demands.

neuroscience↗

Rapidly decreasing phasic dopamine responses precede a hedonic switch during satiation of sodium appetite

HighlightsO_LIPhasic dopamine tracks changing physiological need during sodium appetite C_LIO_LIRapid decreases in dopamine precede the loss of appetitive behavioural responses C_LIO_LITransitions occur abruptly within individuals despite gradual group averages C_LIO_LIDopamine responses track cumulative sodium intake during sodium satiation C_LI Phasic dopamine signalling updates the value of stimuli and actions. Most empirical support for this critical process involves manipulation of extrinsic stimuli (e.g., reward magnitude, reward omission). Yet interoceptive signals clearly influence motivated behaviour. Sodium depletion generates a sodium appetite where the value of sodium increases. How the value of sodium is updated during ingestion and as animals satiate their need remains unknown. Here, we administered sodium chloride solutions via intraoral delivery and measured appetitive behaviour and dopamine release in sodium replete and deplete rats. Two different concentrations of sodium chloride were used to modulate the rate of repletion for sodium deplete rats. Appetitive behaviour was evoked by infusions only when rats were deplete, and this behavioural motif faded away during the session only when high concentration infusions were delivered. Phasic dopamine release in the nucleus accumbens had a similar pattern. We identified transition points for both behaviour and dopamine in the subgroup of rats that reached satiation and found that transitions were sharp, with dopamine decreasing just before behaviour. Moreover, transitions occurred only after enough sodium was infused to replace that typically lost upon depletion. These findings demonstrate that mesolimbic dopamine dynamically updates the value of taste stimuli based on interoceptive signals that relay satiation.

neuroscience↗

Dynamics of feeding behaviour and meal patterning in protein-restricted mice

Of the three dietary macronutrients, protein plays an especially pivotal role in physiological functions. Nevertheless, the behavioural control of protein intake is poorly understood. In this study, we used Feeding Experimentation Devices (FED3s) to examine the structure of ingestive behaviour in mice given access to diets varying in protein content. Adult C57BL/6NRj mice were contact-housed in pairs in custom-made cages with perforated dividers, each having access to an individual FED3 unit. Mice were given ad libitum access to either 20 mg control, non-restricted (NR) pellets (20% casein) or 20 mg protein-restricted (PR) pellets (5% casein) from FED3s on free-feeding mode. Each pellet retrieval event was timestamped [~]24 h/day. All mice experienced both diets for 7 days with order of diet presentation counterbalanced (i.e., NR[->]PR and PR[->]NR). Analysis of dynamics of pellet intake per day revealed that mice that were initially protein-restricted first showed a decrease in pellet intake before increasing on later days and exhibiting a persistent high level of intake once non-restricted diet was available. The group that was initially non-restricted exhibited a blunted response to the same diet manipulation. In addition, we clustered pellet retrieval data into discrete clusters of feeding events and used a mathematical approach to determine the boundary of meals (2-5 pellets), separated from "snacks" (1 pellet) and "feasts" (>5 pellets). We identified alterations in meal patterning in response to diet manipulation with protein restriction increasing "snacking" and leading to increased meal number, and reduced meal size. Moreover, restored access to NR diet, elicited "feasting". These effects depended on the sequence of diets the mice experienced, such that the effects were stronger in initially protein restricted mice compared to those initially non-restricted. In summary, our findings show that manipulation of dietary protein levels affects meal patterning in adult mice.

neuroscience↗

lickcalc: Easy analysis of lick microstructure in experiments of rodent ingestive behaviour

Lick microstructure is a term used in behavioural neuroscience to describe the information that can be obtained from a detailed examination of rodent drinking behaviour. Rather than simply recording total intake (volume consumed), lick microstructure examines how licks are grouped, and the spacing of these groups of licks. This type of analysis can provide important insights into why an animal is drinking, for example, whether it is influenced by taste or affected by consequences of consumption (e.g., feeling "full"). Here we present a software package, lickcalc, that allows detailed microstructural analysis of licking patterns. The software is browser-based and is hosted at https://lickcalc.uit.no or the repository can be downloaded and installed locally. Lick timestamps can be loaded from a variety of formats and different analysis and plotting options allow quality control of data and determining critical parameters for microstructural analysis number and size of lick bursts. Data can be divided into epochs for detailed examination of changes across session. Batch processing and custom configurations are supported. In this manuscript, we demonstrate use of the functions exposed by lickcalc by analysing data comparing lick patterns between mice on a protein-restricted and control (non-restricted) diet. We show that lickcalc allows quality control of the data and uncovering of subtle differences in lick behaviour that are not apparent when just considering the total number of licks. This software makes microstructural analysis accessible to any researchers who wish to employ it while providing sophisticated analyses with high scientific value.

neuroscience↗

RTFED, an open-source versatile tool for home-cage monitoring of behaviour and fibre photometry recording in mice

BackgroundConventional approaches for studying feeding and reward-driven behaviours require frequent animal handling or relocation of animals to specialized chambers, inducing stress, confounding behavioural outcomes, and limiting continuous (24/7) data collection. In recent years, the Feeding Experimentation Device (FED3) has emerged as a major advance, offering programmable modes of operation, affordable costs, and flexibility for investigating a range of feeding and operant behaviours. However, certain limitations prevent researchers from fully harnessing the FED3s capabilities in a user-friendly manner. New methodHere, we present the Realtime and Remote FED3 (RTFED) developed for continuous and online home-cage monitoring of mice, video recording behaviours and fibre photometry recording. ResultsValidation experiments confirm RTFED integrates well with FED3 to log and transmit behavioural events in real-time. It also incorporates event-triggered video capture through USB cameras, providing additional observational depth. Moreover, RTFED handles TTL signals to the fibre photometry system allowing precise behaviour-neural synchronization. Comparison with existing methodsA key strength of RTFED is its easily customizable architecture, enabling researchers to tailor both software and hardware configurations to meet specific experimental objectives. This flexibility, together with features such as remote data logging and email notifications that allow timely adjustments and animal welfare monitoring based on behavioural observations, substantially reduces animal disturbance and researcher intervention and labour. ConclusionsBy offering a cost-effective and modifiable alternative to proprietary commercial solutions, RTFED broadens accessibility, heightens reproducibility, and deepens investigations into feeding and reward-driven behaviours in home-cage settings, ultimately improving the quality and translational relevance of behavioural research. HighlightsO_LIWe enhanced the utility of FED3 with a graphical user interface called RTFED C_LIO_LIRTFED allows real-time and remote monitoring of mouse feeding and operant behaviour C_LIO_LIIt sends notifications in case of device failures or when flagged behaviours happen C_LIO_LIIt records event-triggered videos of defined behaviour C_LIO_LIRTFED relays sub-millisecond TTL outputs for fiber photometry recording C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/666497v2_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@49674eorg.highwire.dtl.DTLVardef@11d4585org.highwire.dtl.DTLVardef@bf2db1org.highwire.dtl.DTLVardef@150f73d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Dietary protein restriction in rats leads to a rapid within-session preference for protein

Evolution has provided species with adaptive behavioural mechanisms that guarantee tight dietary protein regulation. However, an unsolved question is whether the well-established preference for protein-containing food manifested during states of protein restriction is innate or learned. Here, we tackled this problem by maintaining male rats on either a low-protein diet (5% protein, protein-restricted) or a control diet (22% protein, non-restricted) for 9-12 days, and then offered them two novel foods, a protein-containing solution (4% casein) and a carbohydrate-containing solution (4% maltodextrin) during a daily 60-minute free-choice test, repeated for 5 consecutive days. We assessed both the total and cumulative intake of each solution throughout each test, as well as the microstructure of licking behaviour as an index of the solutions palatability. In a second experiment, we exposed a different cohort of rats, before any behavioural test, to the same protein source (i.e., casein) that they would encounter during the free-choice tests, to assess whether familiarity with casein would drive subsequent casein intake even in non-restricted rats. We found that dietary protein restriction leads to a rapid preference (within 16 minutes of first exposure) for a casein-rich solution, and this preference is persistent over subsequent exposures. Increased palatability of protein during initial exposure correlated with protein preference in the restricted rats. Moreover, familiarity with casein did not lead to protein preference in non-restricted rats. This study demonstrates that, when in need of protein, protein preference is a rapid adaptation that requires minimal experience of protein. HighlightsO_LIProtein-restricted rats show a rapid preference for protein over carbohydrate C_LIO_LIThe preference emerges within 5 minutes of exposure to solutions C_LIO_LIIncreased palatability of casein is partially related to preference C_LIO_LIExposure to casein without protein restriction does not lead to preference C_LI

animal behavior and cognition↗

Rapid fluctuations in histamine associated with intake of nutritive and non-nutritive solutions

The neurotransmitter histamine is involved in control of food intake, yet its dynamics during individual feeding episodes remain unexplored. Therefore, we used the novel genetically-encoded histamine sensor, HisLightG, combined with fiber photometry to measure histamine release in two hypothalamic regions critical for the food-suppressive effects of histamine, the paraventricular nucleus of the hypothalamus (PVH), and the ventromedial hypothalamus (VMH). Male mice were tested under different conditions to assess whether hunger, time of day, or the caloric content of the solution they were given affected histamine fluctuations. We found that histamine levels changed rapidly in response to eating. These histamine fluctuations were influenced by experimental conditions, with slightly smaller responses when the test solution was sucralose (both regions) or during the light cycle (PVH only). Notable regional differences were identified, such that in the PVH histamine rebounded to baseline levels, whereas in the VMH histamine remained lower than baseline for at least 10 seconds after licking ceased. In a separate cohort of male and female mice, enhancing histamine tone via administration of a histamine precursor (L-histidine) reduced the number of licks across multiple sucrose concentrations. Together, these findings indicate that histaminergic activity is modulated rapidly during ingestive episodes, and that understanding these release patterns will give insight into histamines role in appetite suppression.

neuroscience↗

Behavioral and neural alterations of the ventral tegmental area by Cafeteria diet exposure in rats

The brain reward system is essential for regulating appetitive and consummatory behaviors in response to various incentive stimuli. Junk food, characterized by its high palatability, is particularly associated with the potential for excessive consumption. While prior studies indicate that excessive junk food intake can impact reward circuitry, the precise mechanisms underlying these effects remain elusive. Furthermore, it is unclear whether the functionality of this neural system is similarly altered in response to other natural rewards. In this study, we used fiber photometry combined with a behavioral reward test to investigate the effects of six weeks of excessive cafeteria (CAF) diet consumption on ventral tegmental area (VTA) neural activity and behavioral responses to food and sexual rewards in female rats. Our findings demonstrate that prolonged exposure to a CAF diet reduced the exploration and consumption of food rewards. These behavioral changes were accompanied by attenuated neural activity in the VTA. Similarly, reductions in VTA activity were observed in response to a sexual partner, although no significant behavioral differences were detected during sexual interactions. Moreover, a two-week reversal diet of standard chow proved insufficient to restore VTA neural activity in CAF-exposed animals, which continued to exhibit decreased VTA responses to both food rewards and sexual partners. Our results suggest that prolonged junk food exposure induces desensitization of the VTA, resulting in reduced responsiveness to natural rewards. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/618156v3_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@63c782org.highwire.dtl.DTLVardef@bf2e28org.highwire.dtl.DTLVardef@16f7ad8org.highwire.dtl.DTLVardef@1ea1235_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

A simple action reduces food intake and obesity in mice

Diets that are high in fat cause over-eating and weight gain in multiple species of animals, suggesting that high dietary fat is sufficient to cause obesity. However, high-fat diets are typically provided freely to animals in obesity experiments, so it remains unclear if high-fat diets would still cause obesity if they required more effort to obtain. We hypothesized that unrestricted and easy access is necessary for high-fat diet induced over-eating, and the corollary that requiring mice to perform small amounts of work to obtain high-fat diet would reduce high-fat diet intake and associated weight gain. To test this hypothesis, we developed a novel home-cage based feeding device that either provided high-fat diet freely, or after mice poked their noses into a port one time - a simple action that is easy for them to do. We tested the effect of this intervention for six weeks, with mice receiving all daily calories from high-fat diet, modifying only how they accessed it. Requiring mice to nose-poke to access high-fat diet reduced intake and nearly completely prevented the development of obesity. In follow up experiments, we observed a similar phenomenon in mice responding for low-fat grain-based pellets that do not induce obesity, suggesting a general mechanism whereby animals engage with and consume more food when it is freely available vs. when it requires a simple action to obtain. We conclude that unrestricted access to food promotes overeating, and that a simple action such as a nose-poke can reduce over-eating and weight gain in mice. This may have implications for why over-eating and obesity are common in modern food environments, which are often characterized by easy access to low-cost unhealthy foods.

animal behavior and cognition↗

Intermittent protein restriction elevates food intake and plasma ghrelin in male mice

Low-protein diets affect body weight, body composition, food intake, and food preferences in mice. Furthermore, single periods of protein restriction can have lasting effects on these parameters. We sought to examine the effect of multiple, short, bouts of protein restriction, relative to long-term maintenance on either a control (NR) or protein-restricted (PR) diet. We found that male mice experiencing intermittent protein restriction (IPR) were indistinguishable from NR mice in terms of body weight and composition, but had food intake and plasma ghrelin as high as mice on PR diet, even when they were returned to control diet. This was not found in female mice. The results of this experiment highlight the importance of diet history on food intake and ghrelin levels in male mice, and the difference in how PR diet might affect male and female mice.

physiology↗

Protein preference and elevated plasma FGF21 induced by dietary protein restriction is similar in both male and female mice

Animals that are moderately protein restricted respond to this dietary stress by increasing consumption of protein-containing foods. This is true in many species, including rodents. Rodent models of protein restriction have typically relied on only male subjects, and there are plausible reasons why female rodents may respond differently to dietary protein restriction. To address this gap in knowledge, the current experiments examined protein preference after two weeks on a 5% protein diet or 20% protein control diet, in male and female mice. We found that female mice, like male mice, increase consumption of 4% casein (protein) relative to 4% maltodextrin (carbohydrate) when presented with both simultaneously. Interestingly, this increased consumption was due to more bursts in females and more licks per burst in males, indicating possible differences in mechanism by which increased intake is achieved. Stage of the estrous cycle did not affect female responses. Moreover, we measured plasma FGF21 - a hormone induced by protein restriction and necessary for protein preference - in male and female mice. Here, we found no statistical differences between protein-restricted males, females in diestrus, or females in proestrus. In non-restricted mice FGF21 levels were low, but significantly higher in females in proestrus than females in diestrus or males. Overall, these experiments highlight the importance of including female subjects in studies of food choice and macronutrient restriction. Highlights- Protein-restricted male and female mice exhibit protein preference - Estrous cycle stage does not influence protein preference - Estrous cycle stage does not affect plasma FGF21 during protein restriction - Non-restricted females in proestrus have higher FGF21 than those in diestrus or males

neuroscience↗

Incertohypothalamic A13 dopaminergic neurons are involved in fine forelimb movements but not reward

Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well-positioned to impact known dopamine-related functions since their descending projections innervate target regions that regulate vigilance, sensorimotor integration and execution. Despite this known connectivity little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects that is independent from reward. A13-DA neurons respond strongly when animals grab and manipulate food items while their inactivation or degeneration prevents animals from successfully doing so - a deficit partially attributed to a reduction in grip strength. In contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Moreover, motivation for food was unaffected as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. These results demonstrate a functional role for A13-DA neurons in prehensile actions that are uncoupled from reward and as such position A13-DA neurons into the functional framework regarding centrally-located DA populations and their ability to coordinate movement.

neuroscience↗

Restriction of dietary protein in rats increases progressive-ratio motivation for protein

Low-protein diets can impact food intake and appetite, but it is not known if motivation for food is changed. In the present study, we used an operant behavioral task - the progressive ratio test - to assess whether motivation for different foods was affected when rats were maintained on a protein-restricted diet (REST, 5% protein diet) compared to non-restricted control rats (CON, 18% protein). Rats were tested either with nutritionally-balanced pellets (18.7% protein, Experiment 1) or protein-rich pellets (35% protein, Experiment 2) as reinforcers. Protein restriction increased breakpoint for protein-rich pellets, relative to CON rats, whereas no difference in breakpoint for nutritionally-balanced pellets was observed between groups. When given free access to either nutritionally-balanced pellets or protein-rich pellets, REST and CON rats did not differ in their intake. We also tested whether a previous history of protein restriction might affect present motivation for different types of food, by assessing breakpoint of previously REST animals that were subsequently put on standard maintenance chow (protein-repleted rats, REPL, Experiment 2). REPL rats did not show increased breakpoint, relative to their initial encounter with protein-rich pellets while they were protein-restricted. This study demonstrates that restriction of dietary protein induces a selective increased motivation for protein-rich food, a behavior that disappears once rats are not in need of protein.

neuroscience↗

Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats

In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in a binge on the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior. Using a novel set of rewarding solutions, we directly compared contextual and gustatory ANC predictors in both food restricted and free-fed Sprague-Dawley rats. Our results indicate that, despite being food restricted, rats are selective in their eating behavior and show strong contextually-driven ANC and do so after fewer training sessions than free-fed animals. These differences mirrored changes in palatability for the less preferred solution across the different sessions as measured by lick microstructure analysis. Moreover, in contrast to previous research, gustatory cues in both food restricted and free-fed rats were sufficient for ANC to develop although this flavor-driven ANC did not relate to a corresponding change in lick patterning. These differences in the lick microstructure between context- and flavor-driven ANC indicate that the motivational processes underlying ANC generated by the two predictor types are distinct.

animal behavior and cognition↗

Distracting stimuli evoke ventral tegmental area responses in rats during ongoing saccharin consumption

Disruptions in attention, salience and increased distractibility are implicated in multiple psychiatric conditions. The ventral tegmental area (VTA) is a potential site for converging information about external stimuli and internal states to be integrated and guide adaptive behaviours. Given the dual role of dopamine signals in both driving ongoing behaviours (e.g. feeding) and monitoring salient environmental stimuli, understanding the interaction between these functions is crucial. Here we investigate VTA neuronal activity during distraction from ongoing feeding. We developed a task to assess distraction exploiting self-paced licking in rats. Rats trained to lick for saccharin were given a distraction test, in which three consecutive licks within 1 second triggered a random distractor (e.g. light and tone stimulus). On each trial they were quantified as distracted or not based on the length of their pauses in licking behaviour. We expressed GCaMP6s in VTA neurons and used fibre photometry to record calcium fluctuations during this task as a proxy for neuronal activity. Distractor stimuli caused rats to interrupt their consumption of saccharin, a behavioural effect which quickly habituated with repeat testing. VTA neural activity showed consistent increases to distractor presentations and, furthermore, these responses were greater on distracted trials compared to non-distracted trials. Interestingly, neural responses show a slower habituation than behaviour with consistent VTA responses seen to distractors even after they are no longer distracting. These data highlight the complex role of the VTA in maintaining ongoing appetitive and consummatory behaviours while also monitoring the environment for salient stimuli.

neuroscience↗

AGE DEPENDENT EFFECTS OF PROTEIN RESTRICTION ON DOPAMINE RELEASE

Despite the essential role of protein intake for health and development, very little is known about the impact of protein restriction on neurobiological functions, especially at different stages of the lifespan. The dopamine system is a central actor in the integration of food-related processes and is influenced by physiological state and food-related signals. Moreover, it is highly sensitive to dietary effects during early life periods such as adolescence due to its late maturation. In the present study, we investigated the impact of protein restriction either during adolescence or adulthood on the function of the mesolimbic (nucleus accumbens) and nigrostriatal (dorsal striatum) dopamine pathways using fast-scan cyclic voltammetry in rat brain slices. In the nucleus accumbens, protein restriction in adults increased dopamine release in response to low and high frequency trains of stimulation (1-20 Hz). By contrast, protein restriction performed at adolescence decreased nucleus accumbens dopamine release. In the dorsal striatum, protein restriction has no impact on dopamine release when performed at adulthood but in adolescent rats we observed frequency-dependent increases in stimulated dopamine release. Taken together, our results highlight the sensitivity of the different dopamine pathways to the effect of protein restriction, as well as their vulnerability to deleterious diet effects at different life stages.

neuroscience↗

Portion size does not influence food consumption in rats

In studies of eating behavior that have been conducted in humans, the tendency to consume more when given larger portions of food, known as the portion size effect (PSE), is one of the most robust and widely replicated findings. Despite this, the mechanisms that underpin it are still unknown. In particular, it is unclear whether the PSE arises from higher-order social and cognitive processes that are unique to humans or, instead, reflects more fundamental processes that drive feeding, such as conditioned food-seeking. Importantly, studies in rodents and other animals have yet to show convincing evidence of a PSE. In this series of studies, we used several methods to test for a PSE in adult male Sprague-Dawley rats. Our approaches included using visually identifiable portions of a palatable food; training on a plate cleaning procedure; providing portion sizes of food pellets that were signaled by auditory and visual food-predictive cues; providing food with amorphous shape properties; and providing standard chow diet portions in home cages. In none of these manipulations did larger portions increase food intake. In summary, our data indicate that a PSE does not appear to be present in rats or, if it is, it is more nuanced, dependent on experimental procedure and/or smaller in size than it is in humans. In turn, these findings suggest that the widely-replicated PSE in humans may be more likely to reflect higher-order cognitive and social processes than fundamental conditioned behaviors.\n\nHighlightsO_LIPortion size effect (PSE) refers to increased food intake induced by large portions.\nC_LIO_LIAlthough widely replicated in human feeding studies, it may not exist animals.\nC_LIO_LIPresence of a PSE in animals would shed light on mechanisms, which are not known.\nC_LIO_LIHere, we find no evidence of PSE in rats under a number of experimental conditions.\nC_LIO_LIThis suggests that the human PSE is more likely due to socio-cognitive processes.\nC_LI

animal behavior and cognition↗

Restriction of dietary protein leads to conditioned protein preference and elevated palatability of protein-containing food in rats.

The mechanisms by which intake of dietary protein is regulated are poorly understood despite their potential involvement in determining food choice and appetite. In particular, it is unclear whether protein deficiency results in a specific appetite for protein and whether influences on diet are immediate or develop over time. To determine the effects of protein restriction on consumption, preference, and palatability for protein we assessed patterns of intake for casein (protein) and maltodextrin (carbohydrate) solutions in adult rats. To induce a state of protein restriction, rats were maintained on a low protein diet (5% casein) and compared to control rats on non-restricted diet (20% casein). Under these dietary conditions, relative to control rats, protein-restricted rats exhibited hyperphagia without weight gain. After two weeks, on alternate conditioning days, rats were given access to either isocaloric casein or maltodextrin solutions that were saccharin-sweetened and distinctly flavoured whilst consumption and licking patterns were recorded. This allowed rats to learn about the post-ingestive nutritional consequences of the two different solutions. Subsequently, during a preference test when rats had access to both solutions, we found that protein-restricted rats exhibited a preference for casein over carbohydrate whereas non-restricted rats did not. Analysis of lick microstructure revealed that this preference was associated with an increase in cluster size and number, reflective of an increase in palatability. In conclusion, protein-restriction induced a conditioned preference for protein, relative to carbohydrate, and this was associated with increased palatability.

neuroscience↗