Beta-Endorphin Modulates the Effect of Stress on Novelty-Suppressed Feeding

Although stress is implicated in the pathophysiology of mood and anxiety disorders, not all individuals who suffer stressful life events develop psychopathology. Differential susceptibility to stress may be influenced by genetically mediated differences in hypothalamic-pituitary-adrenal (HPA) axis activity and moderation of the stress response by the opioid peptide beta-endorphin (beta-E). The present study investigated genetic contributions to coping behavior by examining anxious behavior of transgenic mice with varying capacities to synthesize beta-E [B6.129S2-Pomc(tm1Low)/J; regulated by insertion of a premature stop codon into one or both copies of the proopiomelanocortin (POMC) gene], both under normal conditions and following 3 min of forced swim (FS). Ten minutes after this stress exposure or a control manipulation, acutely food-deprived female and male transgenic mice were subjected to a novelty-suppressed feeding (NSF) test, during which their interaction with an almond slice located in the center of an open field box was measured. There was an interaction between genotype and stress for latency to approach the almond and whether or not the almond was approached, such that mice with low or absent beta-E displayed a stronger aversion to novelty-feeding after stress exposure than did mice with normal levels. These data provide evidence for a moderating effect of beta-E on the behavioral response to stress. Genotypic differences in anxious behavior emerged when mice were stressed prior to behavioral assessment, suggesting that beta-E plays a role in coping behavior. These findings indicate that genetic variability in sensitivity of the beta-E system to stress may contribute, at least in part, to heritable differences in stress reactivity as well as vulnerability to stress-related psychopathology.

Capuchin Monkeys (Cebus apella) Fail to Be Equitable in an Ultimatum Game

The ultimatum game is a commonly used economics game testing humans' sense of fairness. In the game, a "proposer" is given a sum of money and is told they can split it however they want with another human partner. The partner can then either accept the division and both proposer and responder receive the proposed amounts, or the responder can reject the offer and neither player will get anything. Human subjects from most western cultures typically share almost half of an allotted amount, but it remains unknown whether our close primate relatives share this generosity. Recent attempts to present chimpanzees with the ultimatum game have provided inconclusive results, with some studies finding the animals share humans' disposition to behave 'fairly' and others concluding that chimpanzees act selfishly to maximize their own rewards. Capuchin monkeys are known to share many human and chimpanzee social and cooperative behaviors, and this study was the first to present capuchin monkeys with a version of the ultimatum game. Subjects were presented with two differently colored tokens representing different qualitative reward contingencies, one equitable and the other inequitable in favor of the subject proposer. Subjects could select and place one of the tokens in a transfer container. The capuchins were first tested with a "dictator game" where, after the subject monkey selected a token, the rewards (equitable or inequitable) were distributed to the subject and a nearby partner monkey that was not an active participant. The capuchins were then tested on an ultimatum game in which after the subject selected and placed a token in the container, the container was moved to the partner. The partner needed to remove the token and transfer it back to the experimenter for the rewards to be distributed. As such, the partner could reject the subject's offer by refusing to participate and neither would receive a reward. The experiment was conducted to determine if the subject monkey would select the equitable reward option rather than the selfish option in order to maintain the partner's cooperation in the task. Capuchin subjects behaved selfishly and selected the inequitable token significantly more often than the equitable token in both the dictator and ultimatum game with no significant difference in preference between the two games. Interestingly, despite the occasional occurrence of rejection by the partner monkeys (resulting in no reward for the subject), subjects never altered their strategy, continuing to prefer the selfish token. The study may indicate that capuchin monkeys have an inability to judge the effect of their behavior on a conspecific's reward outcome, or an indifference to the outcome if there is an individual cost associated with behaving prosocially.

Assessment of Alcohol Reward in Prairie Voles (Microtus ochrogaster)

The purpose of our study was to assess whether prairie voles find alcohol rewarding. Prairie voles have recently become a species of interest for alcohol studies, which have traditionally used other rodent model species including several different strains of mice and rats. The prairie vole is one of only two known rodent species that readily administers high levels of unsweetened alcohol, implicating it as a potentially effective animal model for studying alcohol abuse. However, voluntary consumption does not necessarily imply that prairie voles find it rewarding. Therefore the purpose of our study was to investigate if alcohol has rewarding properties for prairie voles using three different approaches: place conditioning, flavor conditioning, and immunohistochemistry. Furthermore, we sought to characterize their reward profile and compare it to other commonly used rodent models ¿ C57BL/6 mice, DBA/2J mice, and Sprague-Dawley rats. Place and flavor conditioning are behavioral methods that rely on the learned association between a stimulus and the effects of a drug; the drug of interest in these studies is alcohol. To assess whether prairie voles will demonstrate a conditioned preference for alcohol-paired stimuli, seven place conditioning studies were run that investigated a range of different doses, individual conditioning session durations, and trial durations. Video analysis revealed no difference in the amount of time spent on the alcohol-paired floor, suggesting no conditioned place preference for alcohol. Two flavor conditioning tests were conducted to assess whether voles would demonstrate a preference for an alcohol-paired flavored saccharin solution. Voles demonstrated reduced consumption of the alcohol-paired flavored saccharin solution, regardless of dose or flavor, when alcohol administration occurred after conditioning sessions (p=<0.001). When alcohol was administered before conditioning sessions, no difference in consumption of the alcohol-paired and saline-paired flavored saccharin solutions was seen (p=0.545). Previous studies that have documented similar behavior have hypothesized that this is an example of an anticipatory contrast effect. This theory proposes that prairie voles reduce their intake of a hedonic solution (flavored saccharin solution) in anticipation of later drug administration (alcohol). However, conditioning-based behavioral methods of studying alcohol reward are highly sensitive to the parameters of the conditioned stimulus, thus it is possible that voles will not show preference for alcohol-related stimuli, even if they do find alcohol rewarding. Immunohistochemical analysis supplemented this behavioral data by allowing us to identify specific neural regions that were directly activated in response to the acute administration of alcohol. No difference in the number of activated c-Fos neurons in the Nucleus Accumbens (NAc) core or shell was seen (p=0.3364; p=0.6698) in animals that received an acute injection of alcohol or saline. There was a significant increase in the number of activated c-Fos neurons in the Paraventricular Nucleus of the Hypothalamus (PVN) in alcohol-treated animals compared to saline-treated animals (p=0.0034). There was no difference in the pixel count of activated c-Fos neurons or in the % area activated in the Arcuate Nucleus between alcohol and saline-treated animals (p=0.4523; p=0.3304). In conclusion, the place conditioning studies that were conducted in this thesis suggest that prairie voles do not demonstrate preference or aversion towards alcohol-paired stimuli. The flavor conditioning studies suggest that prairie voles do not demonstrate aversion but rather avoidance of the alcohol-paired flavor in anticipation of future alcohol administration. The preliminary immunohistochemical data collected is inconclusive but cannot rule out the possibility of neuronal activation patterns indicative of reward. Taken together, our data indicate that prairie voles hav