In recent years, worldwide obesity rates have risen dramatically, putting major strain on public health systems and the economy. Obesity is a multifaceted disease and its development can be influenced by a variety of factors including genetic, psychological and environmental influences. One area of current focus in obesity research is that of early life programming. It has been well-established that certain early life factors can impact the physiology and behaviour of the offspring. Because of this, early life programming has become increasingly well studied in order to develop a deeper understanding of how early life can influence obesity development. Another area of interest lies in positive mood. While there has been much research into the effects of negative states such as stress and anxiety on feeding behaviour, there is still very little known about how positive states can influence food choice. Using rat models of prenatal stress, neonatal overnutrition and positive affect, this thesis aimed to investigate the effects of early life and mood factors on feeding behaviour and food choice. Prenatal stress has been extensively studied and is characterised by an enhanced stress response in the offspring. Using two rat models of prenatal stress- social and restraint stress, the effects of prenatal stress on feeding behaviour and food choice in the offspring were examined. In both models, no effects of prenatal stress on either food intake or food choice were observed. However, in both cases the expected alterations to the offspring's stress responses when exposed to an acute stressor were not replicated. This may suggest that models of prenatal stress are not as robust as often cited in the literature. As well as the prenatal environment, the early postnatal environment is also able to influence physiology and behaviour. In terms of obesity, a well-studied model is that of small litter size. Rats from small litters are over-nourished as neonates and because of this illustrate an increased body weight that persists throughout life. While this increase in weight gain has been well-established, there is no evidence examining the impact of neonatal overnutrition on long-term food choice. Therefore, food intake and food choice were measured in small and control litter rats over a 10-week period. When placed on an ad lib diet of bland chow, sucrose and lard, small litter rats consumed significantly more chow than control litter rats, whilst maintaining similar consumption of lard and sucrose. However, when offered a high-fat high-sugar (HFHS) pellet for two hours a day alongside ad lib chow, small litter rats illustrated increased consumption of the HFHS pellet compared to controls. This suggests that small litter rats may be programmed to adjust their food choices to enable them to maintain their increased body weight in comparison to controls. To examine the effects of positive affect on feeding behaviour, ultrasonic vocalisations (USVs, specifically those at 50 kHz) were used as a measure of positive affect in rats. In order to examine whether access to a food reward could induce a positive affect (as measured by an increase in 50 kHz USVs), rats were schedule-fed sweetened condensed milk and USVs measured before, during and after consumption. No differences in 50 kHz USVs were observed suggesting that a palatable food, whilst rewarding, does not alter affective state in the rat. Using heterospecific social contact (a tickling interaction simulating rough and tumble play) to induce positive affect, rats were presented with an hour-long sucrose preference test following social contact in order to examine the impact of positive affect on food choice. While no differences in sucrose consumption were found, a reduced sucrose preference was observed in rats receiving social contact compared to controls, suggesting that positive affect may play a role in mediating food choice. Finally, the effects of fasting (a negative stimulus thought to reduce 50 kHz USVs) and a food reward on motivation for social contact were examined. Both fasting and access to a food reward resulted in no differences in conditioned place preference to receive social interaction. Overall, the results obtained in this thesis implicate both neonatal overnutrition and, for the first time, positive affect as possible mediators of food choice, although further studies are required to fully establish these effects. Importantly, these results also raise questions regarding the reproducibility of some early life models, such as prenatal stress, and highlights the importance of sharing precise experimental protocols across laboratories. Through further investigation of the effects of early life and affective states on food consumption and choice, and the mechanisms behind these, this may enable the development of therapeutic interventions and preventative measures that can help slow, or even reverse, the global obesity epidemic.

Les perturbateurs endocriniens (PE) sont des polluants environnementaux naturels ou fabriqués par l'Homme capables d'interférer avec les systèmes hormonaux endogènes. Parmi ces molécules, le di(2-éthylhexyl) phtalate (DEHP) et le nonylphénol (NP) sont très répandus dans les produits du quotidien et figurent sur la liste des Substances Prioritaires de l'eau. Cependant, peu d'études s'intéressent au contrôle central de la reproduction suite à l'exposition adulte et à de faibles doses de ces PE. L'exposition chronique de souris mâles adultes à ces PE seuls ou combinés montre des altérations à des doses proches de l'exposition environnementale humaine et de la dose journalière tolérable. Nous avons constaté une diminution de l'émission des vocalisations ultrasonores (USV) et de l'attraction des femelles par les mâles exposés au DEHP. Ceci a pu être relié à une diminution de l'expression du récepteur des androgènes dans l'aire préoptique médiane, région clé dans l'expression du comportement sexuel mâle. Ces effets ont été inversés lors de l'arrêt de l'exposition au DEHP. L'exposition au NP augmente l'émission des USV et les nombres de montées, d'intromissions et de poussées pelviennes avant d'atteindre l'éjaculation. Par ailleurs, l'exposition au mélange provoque des altérations comportementales différentes de celles observées pour les molécules isolées. Ces résultats ont permis de mettre en évidence une vulnérabilité du circuit neural régulant l'expression du comportement sexuel à l'exposition à ces PE. Des cibles moléculaires ont également pu être identifiées, particulièrement pour le DEHP, aidant ainsi à la compréhension de leur mode d'action dans le système nerveux central / Endocrine disruptors are natural or man-made environmental pollutants capable of interfering with endogenous hormonal systems. Among these molecules, phthalates and particularly di(2-éthylhexyl) phtalate (DEHP) and nonylphenol are widely present in everyday products and classified as priority substances in the Water Framework Directive. These two molecules are highly studied but few publications address the neural control of reproductive behaviors following adult exposure to low doses of these molecules.Chronic exposure of adult male mice to these two molecules, alone or in combination, showed behavioral alterations at doses close to human environmental exposure and tolerable daily intake. We observed a decreased emission of ultrasonic vocalisations and attraction of receptive females by males exposed to DEHP. These behavioral alterations were related to down-regulation of the androgen receptor in the medial preoptic area, the key region involved in the expression of male sexual behavior. These behavioral and molecular effects were reversed by DEHP exposure arrest. Adult exposure to NP increased the emission of ultrasonic vocalisations and number of mounts, intromissions and pelvic thrusts, without any amelioration of sexual behavior. Interestingly, exposure to both molecules caused behavioral alterations, which are are different from those observed for each molecule alone.Altogether, these results highlight the vulnerability of the neural circuitry underlying sexual behavior to exposure to these molecules. Furthermore, molecular targets have been identified, particularly for DEHP, thereby helping to understand their mode of action in the central nervous system.