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Peptides. Author manuscript; available in PMC Jan 1, 2009.
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Behavioral controls of food intake1

Abstract

Recent conceptualizations of food intake have divided ingestive behavior into multiple distinct phases. Here, we present a temporally and operationally defined classification of ingestive behaviors. Importantly, various physiological signals including hypothalamic peptides are thought to impact these distinct behavioral phases of ingestion differently. In this review, we summarize a number of behavioral assays designed to delineate the effects of hormone and peptide signals that influence food intake on these ingestive mechanisms. Finally, we discuss two issues that we have encountered in our laboratory which may obstruct the interpretation of results from these types of studies. First, the influence of previous experience with foods used in these behavioral tests and second, the importance of the nutrient composition of the selected test foods. The important conclusion discussed here is that the behavioral analysis of ingestion is accompanied by theoretical constructs and artificial divisions of biological realities and the appreciation of this fact can only increase the opportunities of contemporary behavioral scientists to make significant and novel observations of ingestive behaviors.

1. Introduction

Ingestive behavior is a complex process controlled by multiple physiological and psychological mechanisms. Many researchers interested in the biological controls of food intake approach ingestion as a single experimental outcome measurable by total food consumed. While food intake may be the consummate event of this sequence, a rich behavioral literature has described numerous components of this intricate process. Two general categories of behaviors have been elucidated from sequence of events that ultimately lead to ingestion. On one hand, there are behaviors involved in the seeking, locating, and acquiring foods. On the other, are behaviors associated with the act of ingestion itself, including chewing and swallowing. These different behaviors can be generally classified as ‘appetitive’ and ‘consummatory’ and are related to their temporal proximity to the ingestion of food [21].

Importantly, there are numerous central nervous system structures and circuits involved in the control of food intake and energy homeostasis [61, 68, 82]. Peripheral signals, such as leptin and insulin and their receptors are thought to act primarily via hypothalamic circuits containing several distinct neuropeptide systems, which effect changes in ingestive behavior (e.g., [5, 67, 72]. Of these, the orexins (orexin-A), neuropeptide-Y (NPY), melanin-concentrating hormone (MCH), and the melanocortin system have received a great deal of experimental attention over the last several years (e.g., [34, 60, 66, 79, 81, 83, 89]. Each of these peptides is expressed in neurons in the hypothalamus, elicits changes in food intake, and is regulated by energy balance.

Because of the redundancy in systems that can influence food intake, a logical hypothesis is that distinct neuropeptide systems may contribute specifically to the control of different phases of ingestive behavior. For example, some systems might initiate appetitive, pre-ingestive behaviors while other systems elicit hyperphagia by increasing consummatory-phase behaviors. The logic for this hypothesis comes from the observations that appetitive and consummatory phases of ingestive behavior have been reported to be differentially susceptible to various experimental and pharmacological manipulations. For example, Berridge and his colleagues have demonstrated pharmacologically, that the dopaminergic and opioidergic systems are differentially involved in appetitive and consummatory behaviors, which they elegantly describe in theoretical terms of “wanting” and “liking” (see [9, 11, 63] for reviews).

There is a long history of research on the behavioral mechanisms that influence food intake. A full discussion of these psychological and physiological mechanisms could easily fill entire volumes. For simplicity, here, we have chosen to divide these mechanisms into three broad categories that can be defined by their temporal relationship to the ingestion of food: pre-ingestive or appetitive, consummatory and post-ingestive mechanisms.

2. Phases of ingestive behavior

2.1 Pre-ingestive mechanisms

2.1.1 Interoceptive signals

Animals engage in a number of behaviors to find and acquire food. These appetitive or foraging acts are termed “pre-ingestive” since they occur prior to the animal engaging the food directly and consuming it. One hypothesis to be assessed is that hypothalamic peptides act on these appetitive approach and food-seeking behaviors, before the beginning of the more stereotyped consummatory behavior. The initiation of food seeking and ingestion is often considered to result from homeostatic signals that accumulate over the interval since food was last consumed. Specifically, food deprivation is thought to generate homeostatic signals related to the gradual depletion of energy stores (e.g., [53]), and these signals may make animals more likely to engage in appetitive behaviors that ultimately lead to food consumption. The first requirement for changes in physiological systems related to food deprivation to be able to effect food-seeking and other pre-ingestive behaviors is that animals must be able to detect these changes. In fact, there is compelling evidence, using Pavlovian conditioning techniques, demonstrating that animals can learn to respond to the presence or absence of these internal signals.

We have developed and extensively used a paradigm for assessing this process [2224]. In this deprivation-discrimination procedure, rats are trained such that one level of food deprivation (e.g., 24 hr) is always associated with the delivery of a specific reinforcer while another level of deprivation (e.g., 0 hr) is not. Physiological signals related to being 24-hr food deprived then become associated with the subsequent presentation of reinforcement and being 24-hr food deprived causes the animal to anticipate the reinforcement presentation. Discrimination is achieved to the extent that an animal makes more anticipatory responses (i.e., behaviors appropriate for preparing for the reinforcement) when 24-hr food deprived (reinforced condition) than when 0-hr deprived (non-reinforced condition). Importantly, in these experiments, another group of rats receives the reverse contingency between deprivation and reinforcement (i.e., reinforcer presented when 0-hr food deprived, but not when 24-hr food deprived).

Using both appetitive (peanut oil, sucrose pellets) and aversive reinforcements (foot-shock), we have found that rats readily solve this discrimination (e.g., [23, 26]). There are two important implications of this. The first is that food deprivation (or its absence) produces reliable internal signals that the animal can detect and use to influence its behavior. The second is that once rats have been trained to respond differentially to these signals, they can then be assessed for generalization to pharmacological manipulations that influence food intake.

A key question for our research is whether or not administration of exogenous compounds that change food intake will elicit patterns of responding similar to those seen after periods of food deprivation or food repletion. That is, we seek to assess whether such manipulations might play a role in the production of interoceptive sensory stimuli that underlie the psychological constructs of “hunger” and “satiety” and contribute to the altered behavioral responses to food and food-related stimuli. In this respect, we define “hunger” and “satiety” 1) operationally as periods of 24- and 0-hr food deprivation, respectively, and 2) functionally as the consequent physiological events of different degrees of food deprivation (e.g., associated changes in peripheral signals like leptin, insulin, and glucose, as well as central neuropeptides such as NPY. The reliance on behavioral techniques unrelated to food intake to answer these questions is crucial because 1) we seek to understand what physiological systems underlie specific psychological states such as hunger or satiety, and 2) because they help reduce the potential confounds encountered when tests rely solely on measures of food intake (see [22, 27]).

Employing this type of deprivation-discrimination in a recent experiment, we observed that intracerebroventricular administration of melanocortin agonists causes trained rats to respond as if they were 0-hr food deprived and, conversely, that melanocortin antagonists elicit responding like that following 24-hr food deprivation. Additionally, we have also demonstrated that the orexigenic stomach-derived hormone ghrelin elicits conditioned responding like that observed following a period food deprivation and that the gut peptide cholescystokinin and the adipocyte hormone leptin, both of which act to reduce food intake, generalize to a state of 0-hr food deprivation [28, 29, 52]. On the other hand, administration of NPY does not elicit behavior similar to 24-hr food deprivation in this paradigm, suggesting that this peptide acts via mechanisms other than inducing an interoceptive state of “hunger” [51, 73].

2.1.2 Appetitive behaviors

Another well-validated procedure for evaluating the effects of pharmacological manipulations on appetitive behaviors is also based in Pavlovian conditioning. In this experimental paradigm, animals are trained to associate a discrete cue with food presentation. In one version of this procedure, rats are trained to expect a small drop of peanut oil following the presentation of one stimulus (e.g., a light) and to expect a small drop of a sucrose solution following the presentation of a different stimulus (e.g., a tone). The animals must then learn to approach a food cup to obtain the oil or the sucrose when the appropriate stimulus is presented [2, 7, 25]. After extensive training, the animals are treated with a pharmacological manipulation that is known to alter food intake, and they are given a test trial in which the “oil” and the “sucrose” stimuli are presented, but no oil or sucrose is delivered. Whether or not the animal approaches the food cup during each specific stimulus (oil or sucrose) is the dependent variable of interest. The extinction condition (i.e., no oil or sucrose available) during the test trial is an important feature of this paradigm. This allows us to conclude that any changes in responding are indicative of pre-ingestive mechanisms affected by the peptide of interest and are not confounded by changes in palatability or energy intake.

In addition to affecting overall approach behavior toward food-paired stimuli, different peptides and hormones might be critically involved in the selection of specific macronutrients. The use of multiple cue-nutrient pairings has allowed our lab to use this paradigm to assess hypotheses about how specific hypothalamic neuropeptides alter responses to sucrose and oil-specific stimuli while simultaneously assessing the effect on general appetitive behaviors. Data from our lab using this paradigm indicate that NPY appears to have a general effect to increase appetitive behavior in response to the context in which both foods were provided, while appetitive behavior following administration of the melanocortin antagonist agouti-related peptide (AgRP) is nutrient-specific, increasing in response to the oil-paired cue and decreasing in response to the sucrose-paired cue[2, 78].

2.1.3 Motivational mechanisms

The Pavlovian paradigm described above is an ideal tool for assessing the appetitive effects of hypothalamic peptides involved in food intake when animals are faced with cues previously associated with the delivery of food. However, those studies require only minimal effort to obtain the food reinforcer and do not address possible effects of these peptides on an animal’s willingess to work for food. An operant progressive ratio response schedule [14, 37], allows determination of the degree of effort a rat will expend to earn a reinforcer and, as commonly employed in the drug self-administration literature, is often considered a measure of the animal’s “motivation” to obtain that particular reinforcer [65]. In this paradigm, the number of responses required to obtain each morsel of food is progressively increased during a meal. As expected, food deprivation increases the number of responses rats will make to obtain food whereas having just eaten decreases that number [47]. This paradigm can therefore be used to compare the “motivational” effects of a hormone or peptide of interest to the effects of different levels of food deprivation. This use of the paradigm has demonstrated that NPY is capable of producing increases in operant responding and that response levels are similar to 36–48 hr food deprivation [49, 50]. Orexin-A and peripheral insulin also increase progressive ratio breakpoints for sucrose, although not to the same extent as NPY or significant (i.e., 24-hr or greater) food deprivation [50, 75]. On the other hand, direct central administration of the adiposity signals insulin and leptin, which both reduce intake of freely available food, also reduce operant responding for a sucrose reinforcer [38].

In addition, we are currently using this paradigm to assess the effects of hypothalamic neuropeptides on responding for different macronutrients (e.g., carbohydrates vs. fats). Data from our lab suggest that AgRP selectively increases operant responding for fats, but not carbohydrates [78]. Other data using this paradigm show that a cannabinoid receptor agonist increases and an antagonist decreases PR responding for a sweet mixed-nutrient reinforcer, as well as one that is 100% fat, but with far more pronounced effects on the sweet food [80].

2.2 Consummatory mechanisms

2.2.1 Taste and palatability

Another major division of the behavioral and psychological controls of food intake comes into play during the ingestive behavior itself. Palatability (defined here as an indication of food’s hedonic value) influences both the amount and type of food that is ingested [810]. For example, it is well known that even non-caloric solutions will elicit drinking behavior in sated rats if they are made to taste sweet [18]. It is possible that one set of physiological signals might reduce ingestion by making foods less palatable. Conversely, other signals might increase the ability of a particular taste to elicit consumption. In one example of this, food deprivation has been shown to alter preferences for mineral oil relative to saccharin, both non-caloric substances, but with drastically different orosensory properties that mimic those of fats and carbohydrates (i.e, oily versus sweet) [58].

Consistent with this general idea, some hypothalamic peptides (e.g., hypothalamic melanocortins) project to CNS areas important for taste processing (nucleus of the solitary tract) and for food hedonics, including the ventral tegmental area, nucleus accumbens, and substantia nigra [54, 56, 88]. Further, leptin receptors are directly expressed in the VTA, leptin deficiency leads to mesolimbic dopamine dysfunction and leptin, like being sated, has been found to regulate the hedonic qualities of brain self-stimulation [39, 42, 43]. The implication of this collective evidence is that the effect of leptin or its effector neuropeptides on food intake may be due to the modulation of taste-related properties, or “palatability” during the behavior itself. In fact, a recent study found that centrally administered orexin-A, MCH and NPY increased intake of saccharin, while AgRP, ghrelin and dynorphin had no effect [44]. These results suggest that the former peptides increase taste-based consummatory behaviors independent of calories, while the latter may be more dependent on post-ingestive mechanisms.

Since food must contact receptors on the tongue in order for palatability to be assessed, and this generally results in swallowing of the food, post-ingestive (i.e., gastrointestinal) factors can easily confound interpretations of experiments designed to determine the specific effects of palatability. A procedure known as “sham feeding” is one method that can be used to assess the effects of taste and orosensory stimulation independent of post-ingestive effects. The sham feeding method involves surgical implantation of a fistula in the stomach, which can be opened during testing to allow food to drain out of the stomach, eliminating post-oral stimulation [87]. Manipulations that alter intake during sham feeding, therefore, can be attributed to effects on the orosensory characteristics of the ingested solution. Central administration of NPY enhanced sham feeding of a sucrose solution to an even greater extent than real feeding, leading to the conclusion that the NPY acts primarily via consummatory mechanisms to increase food intake [77].

While eliminating confounding post-ingestive effects, the sham feeding technique still requires animals to locate and actively ingest the selected food. A clever technique to separate the consummatory from the pre-ingestive phase is the intraoral intake paradigm. This procedure allows for direct assessment of liquid (e.g., 10% sucrose) intake without the potential confounds of general activity or differences in appetitive approach behaviors. Briefly, rats receive an implanted intra-oral catheter through which small amounts of flavored solutions can be infused directly into the oral cavity. In this way, the experiment can circumvent the usual pre-ingestive behaviors such as the approach to a bottle, and instead directly assess the consummatory effects of a particular manipulation. Further, the technique can be used in combination with intake from a bottle on the homecage to dissociate the specific pre- and ingestive behavioral effects of a treatment. For example, treatments that increase bottle-intake but not intra-oral intake are thought to be involved in appetitive or pre-ingestive behaviors. In an experiment using the intraoral intake paradigm, Seeley and colleagues [74] demonstrated that centrally administered NPY increased rats’ intake of sucrose from a bottle on the homecage, but had no effect on sucrose delivered directly into the oral cavity (intraoral administration). Based on these observations, Seeley et al., concluded that NPY exerted its orexigenic effects predominantly via appetitive or pre-ingestive, rather than consummatory, mechanisms.

2.2.2 Flavor Learning

Additional evidence supporting the role of taste in the control of intake comes from experiments that examine learning about flavors. Numerous experiments indicate that the acceptance or avoidance of flavors can be manipulated through conditioning procedures [17, 19, 35, 69, 71]. For example, rats will increase their intake of a less preferred flavor solution (such as quinine) if its presentation has historically been followed by another, preferred flavor solution [13]. In other kinds of experiments, delivery of a flavor that is normally preferred can support the learning of a conditioned place preference in rats [30]. In these paradigms, rats are given an equal amount of experience in two novel contexts, each of which has a drinking tube. In one context the drinking tube delivers water or a non-preferred solution. In the other, the tube delivers a highly preferred sucrose solution. At a later test, rats are given a choice between the two contexts but without access to the drinking tubes. The common finding is that they spend more time in the context where they had received the sucrose solution. These data indicate that flavor itself can be a powerful stimulus capable of supporting learning. Indeed, we have recently observed that that the adipocyte hormone leptin reduces the reinforcement potency of sweet tastes to elicit a conditioned place preference. In that experiment, food-deprived rats were given access to sucrose in a conditioned place preference paradigm after receiving leptin or saline. As occurs when rats are trained just after eating and are sated, leptin attenuated subsequent preference for the chamber that contained sucrose. Importantly, the amount of sucrose consumed during training was extremely small (1.5 kcal), strongly implicating taste rather than calories as the key aspect of the stimulus in the paradigm [40].

2.3 Post-ingestive mechanisms

After an animal has consumed food and is operationally “sated,” post-ingestive processes are thought to be engaged which influence subsequent food intake. It is well known that animals learn about these post-ingestive consequences of eating [27, 33, 35, 57, 70]. One early example of post-ingestive learning is the conditioned taste aversion. When rats experience visceral illness after ingestion of a novel flavor, the likelihood that this flavor will be consumed again is greatly decreased [45]. In terms of the present analysis, an animal in this situation has learned that the post-ingestive consequences of eating a particularly flavored food are negative. Analogously, animals can also learn about the positive post-ingestive consequences of food intake. For example, rats can learn to associate foods or tastes with specific nutrient or caloric content [33, 41, 59, 64, 76]. This kind of learning can then influence subsequent food choice decisions. Generally, flavors paired with more calories will be preferred relative to those paired with fewer calories [1]. However, particularly high levels of nutrient density will reduce intake of an associated flavor, a phenomenon known as conditioned satiety [12]. Deprivation state can also affect these flavor preferences, with preferences for flavors paired with more caloric foods enhanced by food deprivation and depressed under states of satiety [36, 86].

One way in which learning about the post-ingestive effects of particular foods has been conceptualized is termed “incentive value”. According to this view, the magnitude of the postitive post-ingestive consequences of ingestion is a function of deprivation state. Therefore, animals assign incentive values to specific foods based upon the degree of food deprivation present when the foods are consumed [3, 4, 31, 32]. During fasting, consumption of foods, particularly novel foods, will lead to assignment of a higher incentive value for that food than when the same food is consumed when an animal is sated. Over time, multiple experiences with foods under a variety of deprivation conditions will ultimately allow an animal to modulate their intake of a variety of foods based on the anticipated post-ingestive effects, or the incentive value they have assigned, given their deprivation level at a particular eating occasion. However, if an animal encounters a particular food only when food deprived, that food will maintain a consistently higher incentive value than foods that are sampled under both low and high deprivation. A higher incentive value, even in the absence of food deprivation, can subsequently elicit both increased food intake and increased appetitive approach behaviors [3].

Based on this notion, we have developed an experimental paradigm designed to assess the effects of hypothalamic peptides on the learning of these flavor → post-ingestive relationships. In this paradigm, animals are trained to associate a cue with a specific food (e.g., sucrose) under one deprivation condition. Animals are then exposed to this same food under either the same deprivation condition, a novel condition, or after being treated with a peptide of interest. They are then tested for their responding to the food-paired cue under the novel deprivation condition. Having been previously exposed to the food under this condition alters the animals responding during the test relative to those animals that were always given the food in the same deprivation condition, as the former group hashad the opportunity to learn about the post-ingestive effects of the food under this state. The responding of the group treated with the peptide of interest (in the original deprivation condition) can then be compared to the animals in both groups to determine the effect of this peptide to alter what is learned about the post-ingestive consquences of the food.

The hypothalamic melancortin peptide, alpha-melanocyte stimulating hormone (α-MSH), seemed an obvious candidate to test in this paradigms, as it reportedly increases the efficiency of some forms of learning and memory [46, 62, 84, 85]. With respect to learning about post-ingestive consequences, we observed that the α-MSH analogue MTII (which potently reduces food intake) was unable to support post-ingestive learning like that following the ingestion of food in a non-deprived state. These data are consistent with several general ideas: 1) That the processes underlying consumption of food and learning about the post-ingestive effects of food intake may be genuinely separable and 2) That specific neuropeptide systems might be involved in one, but not another of the processes.

3. Complications in differentiating the phases of ingestion

Obviously one important goal for these different behavioral techniques and conceptualizations is to elucidate the different physiological and biological controls of specific phases of ingestion. However, there are a number of issues that can complicate the interpretations of experimental results using several of the above paradigms. We would like to highlight two of these issues here: the effect of previous experience and the effect of test food selection.

3.1 Previous experience

As have others, we have hypothesized that specific hormones and peptides might play critical roles in specific ingestive processes. Multiple peptide systems have received significant attention along these lines. For example, neuropeptide-Y (which elicits robust increases in food intake) has previously been suggested to play an important role in the initiation of pre-ingestive or “appetitive” behaviors of food intake, but not in the cosummatory phase of ingestion. As described above, a previous study conducted by Seeley et al. [74] concluded that the NPY acts through pre-ingestive, or appetitive, mechanisms, but not consummatory mechanisms, to increase food intake due to its ability to increase sucrose consumption from a lick-spout, but not when the solution was delivered intraorally.

We recently sought to replicate and extend these findings to other hypothalamic peptide systems [6]. The purpose of those experiments was to assess the effects of NPY, MCH, and orexin-A to elicit selectively appetitive or consummatory ingestive behaviors. Obviously the elucidation of distinct ingestive behavior phases for each candidate peptide would be of significant importance and value. Based on the previous research [74], we predicted that at least the effects of NPY would be limited to appetitive (pre-ingestive) driven sucrose intake (i.e., intake from a bottle on the homecage). However, to our surprise, we failed to confirm this hypothesis and instead observed that all neuropeptides under investigation were quite effective to increase intake of sucrose delivered directly into the mouth.

Unfortunately, this discrepancy seemed to present serious interpretative difficulty for either 1) the role of neuropeptides in such discrete behaviors, or 2) the existence of such “phases” of ingestion at all. On closer inspection, however, we noted an important difference between the studies: Prior to intraoral testing, Seeley [74] administered approximately 10 sessions of intraoral sucrose solution to habituate the rats to the experimental apparatus and procedure. In our recent study, no intraoral pretraining was administered. Thus, the rats’ first experience with sucrose was on the first day of testing with intracerebroventricular peptides. Importantly, we noted that comparison of the data from each study revealed that the previous [74] saline baseline was greater than twice that we observed on our first day of sucrose delivery. In this case, an unfortunate experimental error lead to a novel observation – the ability to interpret different effects of consummatory and appetitive responding may depend greatly on the previous experience of experimental subjects.

3.2 Test food composition

In any experimental analysis of food intake or feeding-related behaviors, a specific food or foods must be selected in order to conduct the test(s) of interest. In many cases, test foods are chosen on the basis of availability, cost or convenience. Often, sucrose is used as a test food because it is easy to prepare in solutions of various concentrations, it is easily measured when delivered via a graduated sipper tube, and it is readily accepted by rodents. While the experiment described above cautions researchers regarding the effects of animals prior experiences with test foods, we are gathering further data in our lab that suggest that the nutrient composition hould also be taken into consideration when selecting foods for many of these behavioral assays.

Recently, our laboratory has been interested in the effects of hypothalamic feeding peptides on “reward”-related behaviors (meaning behaviors related to the palatability, hedonic, or other non-homeostatic motivational mechanisms). Specifically, previous evidence indicats that melanocortin peptides may act in mesolimibic regions to affect both food and non-food reward [15, 16, 48, 55]. As discussed above, altering the motivational and rewarding aspects of food stimuli can strongly influence pre-ingestive behaviors. Thus, we set out to assess the effects of AgRP, an endogenous melanocortin receptor antagonist known to potently increase food intake, on operant progressive ratio responding and conditioned place preference [20, 78]. Using sucrose as the reinforcer of choice yielded no effect of AgRP treatment on operant responding, a result which would lead us to conclude that melanocortins do not act to influence food intake by affecting motivational mechanisms. In the conditioned place preference test, animals given saline during training sessions displayed a significant preference for the environment paired with sucrose, while AgRP-treated animals showed no significant environment preference.

However, we also chose to conduct each of these experiments with an alternate reinforcer (peanut oil in the operant test and high-fat diet in the place preference study). In both cases, we observed substantially different results. Under these conditions, AgRP treatment increased operant responding for peanut oil, while a preference for the high-fat-paired environment was equivalent for both AgRP- and saline-treated animals. Clearly, these experiments indicate that the effects of melanocortins on appetitive behaviors can differ based on the nutritional composition of the food in question. Even more important, however, is the general observation regarding the importance of test-food selection when assessing the effects of neuropeptides on the different phases of ingestive behavior.

4. Conclusions and extensions

The history of research and behavioral analysis of ingestion spans many decades. Intricate theories and divisions of distinct behavioral ingestive phases have received much popularity and recent discoveries in neuroscience have bolstered support for these ideas. Nonetheless, our recent observations strongly indicate that behavioral work may be steeped in methodologies that foster one interpretation over another. For example, if we had recently included pre-exposure to the intra-oral administration paradigm, we might not have observed that NPY and other hypothalamic peptides increased IO administration, relative to vehicle treatment. Furthermore, had we used only sucrose as a reinforcer in recent experiments on operant responding and conditioned place preference, we would have come to vastly different conclusions regarding the effects of AgRP on motivation and reward than when a fat-based reinforcer was included. The important point is that while theories and conceptualizations of ingestive behaviors have been intricately developed and supported by myriad experimental data, they are theories and concepts nonetheless. They do not completely represent the true intricacies of the physiological and biological systems that give rise to the behaviors which are being recorded. These behaviors are influenced by the prior experiences of the animal and environmental variables often unnoticed by experimenters. We suggest that the study of biological underpinnings of ingestion be coupled with consideration of the impact of these factors on the behavioral controls of food intake.

Acknowledgments

This work was supported by National Institutes of Health grant DK066223 to S.C. Benoit.

Footnotes

1This work was an invited review from the recipient of the 2007 Gayle A. and Richard D. Olson Prize for meritorious behavioral research.

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