Andrea L. Tracy

Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat

Recent studies indicate that decreased central dopamine is associated with diet-induced obesity in humans and in animal models. In the current study, the authors assessed the hypothesis that diet-induced obesity reduces mesolimbic dopamine function. Specifically, the authors compared dopamine turnover in this region between rats fed a high-fat diet and those consuming a standard low-fat diet. The authors also assessed behavioral consequences of diet-induced obesity by testing the response of these animals in a conditioned place paradigm using amphetamine as a reinforcer and in an operant conditioning paradigm using sucrose reinforcement. Results demonstrate that animals consuming a high-fat diet, independent of the development of obesity, exhibit decreased dopamine turnover in the mesolimbic system, reduced preference for an amphetamine cue, and attenuated operant responding for sucrose. The authors also observed that diet-induced obesity with a high-fat diet attenuated mesolimbic dopamine turnover in the nucleus accumbens. These data are consistent with recent hypotheses that the hormonal signals derived from adipose tissue regulate the activity of central nervous system structures involved in reward and motivation, which may have implications for the treatment of obesity and/or addiction.

The hippocampus and motivation revisited: appetite and activity

After reviewing the available data regarding the various effects of manipulating (e.g. lesions, chemical or electrical stimulation) the hippocampal formation, Jarrard concluded that this structure likely played a role in motivated behaviors, specifically in general behavioral activation and incentive motivation. Since that time there have been technical advances in lesion techniques and conceptual advances in theories of motivation and learning. Here, we present more recent data that demonstrates the effects of hippocampal lesions on general activity, the utilization of interoceptive state cues, ingestive behaviors, and appetitive responding. We critically evaluate several theories of hippocampal function that have been proposed to explain these data, including the hippocampus as an inhibitor of general activation, as a processor of energy state signals and as a mediator of reward valuation. Finally, we propose that these findings may also be accounted for based on a role for the hippocampus in the learned inhibition of appetitive behaviors. We conclude that, while the specific mechanism of hippocampal involvement may not yet be determined, it is clear that this structure is involved in food-related behaviors and we caution researchers to consider this as a possible confound in studies of learning and memory processes.

The melanocortin antagonist AgRP (83-132) increases appetitive responding for a fat, but not a carbohydrate, reinforcer.

Consumption of a diet high in fat is a risk factor for a number of health problems, including obesity, type 2 diabetes and cardiovascular disease. Considerable pharmacological, genetic, and molecular evidence suggests that the hypothalamic melanocortin system plays a critical role in the control of food intake and body weight and, specifically, in fat ingestion. Administration of a melanocortin antagonist, agouti-related peptide (AgRP) (83-132) selectively increases intake of pure fat and high-fat mixed diets. Here, we examined possible mechanisms for this fat-specific effect of AgRP (83-132). In Experiment 1, we determined that intracerebroventricular administration of AgRP (83-132) selectively increased operant responding for a peanut oil, but not a sucrose, reinforcer when tested under a progressive ratio schedule. Experiment 2 employed a Pavlovian conditioning paradigm, in which icv AgRP enhanced appetitive responding toward stimuli that had previously been paired with peanut oil and reduced responding toward stimuli previously paired with sucrose, in the absence of consumption of either macronutrient. Finally, in Experiment 3, we tested the hypothesis that the MC system acts in anticipation of a fat consumption and found that hypothalamic AgRP mRNA was slightly, though not significantly, elevated in an environment predicting fat availability relative to one predicting carbohydrate availability. Collectively, these data indicate that, in addition to increasing free intake of dietary fats, AgRP (83-132) promotes responding for the opportunity to consume a fat reinforcer, as well as appetitive responding to fat-paired stimuli in the absence of ingestive stimulation. These results suggest a possible role for AgRP in the increased fat intake associated with obesity.

Novel functions of orexigenic hypothalamic peptides: From genes to behavior

The regulation of energy balance depends on the precise co-ordination of multiple peripheral and central systems. Much recent research has highlighted the importance of behavioral mechanisms is this control and suggested that the regulation of body weight shares central nervous system pathways in common with other complex behaviors, including learning and drug addiction. We present a brief review of some of this work and highlight the novel functions for central orexigenic neuropeptides. We review evidence that organisms engage in critical regulatory behaviors before and after ingestion has occurred. Additional evidence supports the idea that appetitive mechanisms are engaged that are critical for the regulation of intake during the act of ingestion. We briefly discuss the recent work on the potential role for central nervous system reward centers, how those might be critically linked to the central regulation of food intake, and how they may be dysregulated by the abundance of highly palatable, energy-dense foods.

Roux en Y Gastric Bypass Increases Ethanol Intake in the Rat

Roux en Y gastric bypass (RYGB) surgery is currently the most effective therapy employed to treat obesity and its associated complications. In addition to weight loss and resolution of metabolic syndromes, such as diabetes, the RYGB procedure has been reported to increase alcohol consumption in humans. Using an outbred rodent model, we demonstrate that RYGB increases postsurgical ethanol consumption, that this effect cannot be explained solely by postsurgical weight loss and that it is independent of presurgical body weight or dietary composition. Altered ethanol metabolism and postsurgical shifts in release of ghrelin were also unable to account for changes in alcohol intake. Further investigation of the potential physiological factors underlying this behavioral effect identified altered patterns of gene expression in brain regions associated with reward following RYGB surgery. These findings have important clinical implications as they demonstrate that RYGB surgery leads directly to increased alcohol intake in otherwise alcohol nonpreferring rat and induces neurobiological changes in brain circuits that mediate a variety of appetitive behaviors.

Characterization of attenuated food motivation in high-fat diet-induced obesity: Critical roles for time on diet and reinforcer familiarity.

Prior work using animal models to study the effects of obesogenic diets on food motivation have generated inconsistent results, with some reporting increases and others reporting decreases in responding on food-reinforced tasks. Here, we identified two specific variables that may account for these discrepant outcomes - the length of time on the obesigenic diet and the familiarity of the food reinforcer - and examined the independent roles of these factors. Time on diet was found to be inversely related to food motivation, as rats consuming a 40% high-fat diet (HFD) for only 3weeks did not differ from chow-fed rats when responding for a sucrose reinforcer on a progressive ratio (PR) schedule, but responding was suppressed after 6weeks of ad lib HFD consumption. Explicitly manipulating experience with the sucrose reinforcer by pre-exposing half the rats prior to 10weeks of HFD consumption attenuated the motivational deficit seen in the absence of this familiarity, resulting in obese rats performing at the same level as lean rats. Finally, after 8weeks on a HFD, rats did not express a conditioned place preference for sucrose, indicating a decrement in reward value independent of motivation. These findings are consistent with prior literature showing an increase in food motivation for rats with a shorter time consuming the obesigenic diet, and for those with more prior experience with the reinforcer. This account also helps reconcile these findings with increased food motivation in obese humans due to extensive experience with palatable food and suggests that researchers engaging in non-human animal studies of obesity would better model the conditions under which human obesity develops by using a varied, cafeteria-style diet to increase the breadth of food experiences.

The role of the hypothalamic melanocortin system in behavioral appetitive processes

Much evidence suggests that the hypothalamic melanocortin (MC) system plays an important role in the control of food intake. However, investigations of the potential behavioral mechanisms have been limited to measures of aversion. The purpose of the present experiment was to assess whether other behavioral consequences of administration of MC peptides were similar to those produced by 0- or 24-h food deprivation, respectively. Rats were first trained while food deprived that a tone predicted the delivery of peanut oil. They then received exposure to oil under food deprivation, satiation, intra-third-cerebroventricular (i3vt) infusion of MTII (a potent MC agonist) or SHU-9119 (a potent MC antagonist). All rats were then tested during extinction for levels of responding to the tone under food satiation. Previous results demonstrated that sated exposure reduces subsequent test responding to the tone. During the present extinction test, rats that received sated exposure exhibited reduced responding to the tone, relative to rats that received deprived exposure. Unlike satiation, rats that received exposure after MTII exhibited continued high levels of responding to the tone. Further, rats that received SHU-9119 exhibited a small reduction in responding. These data suggest that MTII and SHU-9119 do not influence intake via the same mechanisms as hunger and food satiation, respectively.

Behavioral controls of food intake

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.

Comparison of Nutritive and Nonnutritive Stimuli in Intestinal and Oral Conditioned Taste Aversion Paradigms

The intestinal taste aversion paradigm has previously demonstrated that animals could orally discriminate between carbohydrate and fat subsequent to pairing a gastrointestinal (GI) infusion of 1 nutrient with lithium chloride (LiCl), whereas they could not discriminate between 2 nonnutritive flavors (A. L. Tracy, R. J. Phillips, M. M. Chi, T. L. Powley, & T. L. Davidson, 2004). The present experiments assessed the relative salience of nutritive and nonnutritive stimuli when presented either intestinally or orally. Two compound stimuli, each comprising 1 nutrient and 1 nonnutritive flavor, were presented in training and were paired with LiCl or saline. Subsequent oral intake of the nutrients alone, the flavors alone, or the compounds was measured. Results showed that rats discriminated both nutrients and flavors independently after GI or oral training, whereas the compounds were discriminated only after oral training, indicating substantive differences in the processing of these stimuli. This suggests that nutrient activation of the GI tract may potentiate learning about nonnutritive flavors analogously to taste-potentiated odor conditioning. The ability to learn about the oral properties of stimuli in the GI tract suggests a new account of delayed taste aversion learning as well as learning about the positive nutritive consequences of food consumption.

Aversion learning can reduce meal size without taste avoidance in rats.

Nausea and aversive food responses are commonly reported following bariatric surgery, along with post‐surgical reduction in meal size. This study investigates whether a meal size limit can be conditioned by associating large meals with aversive outcomes.