Food restriction-induced changes in motivation differ with stages of the estrous cycle and are closely linked to RFamide-related peptide-3 but not kisspeptin in Syrian hamsters.

We tested the hypothesis that the effects of food restriction on behavioral motivation are mediated by one or both of the RFamide peptides, RFamide-related peptide-3 (RFRP-3) and kisspeptin (Kp) in female Syrian hamsters (Mesocricetus auratus). Female hamsters fed ad libitum and given a choice between food and adult male hamsters are highly motivated to visit males instead of food on all four days of the estrous cycle, but after 8days of mild food restriction (75% of ad libitum intake) they shift their preference toward food every day of the estrous cycle until the day of estrus, when they shift their preference back toward the males. In support of a role for RFRP-3 in these behavioral changes, the preference for food and the activation of RFRP-3-immunoreactive (Ir) cells in the dorsomedial hypothalamus (DMH) showed the same estrous cycle pattern in food-restricted females, but no association was observed between behavior and the activation of Kp cells in the hypothalamic arcuate nucleus or preoptic area. Next, we tested the hypothesis that food-restriction-induced activation of RFRP-3-Ir cells is modulated by high levels of ovarian steroids at the time of estrus. In support of this idea, on nonestrous days, mild food restriction increased activation of RFRP-3-Ir cells, but failed to do so on the day of estrus even though this level of food restriction did not significantly decrease circulating concentrations of estradiol or progesterone. Furthermore, in ovariectomized females, food-restriction-induced increases in activation of RFRP-3-Ir cells were blocked by systemic treatment with progesterone alone, estradiol plus progesterone, but not estradiol alone. Central infusion with RFRP-3 in ad libitum-fed females significantly decreased sexual motivation and produced significant increases in 90-minute food hoarding, in support of the hypothesis that elevated central levels of RFRP-3 are sufficient to create the shift in behavioral motivation in females fed ad libitum. Together, these results are consistent with the hypothesis that high levels of ingestive motivation are promoted during the nonfertile phase of the estrous cycle by elevated activation of RFRP-3-Ir cells, and RFRP-3-Ir cellular activation is modulated by ovarian steroids around the time of estrus, thereby diverting attention away from food and increasing sexual motivation.

RFamide-related Peptide-3 and the Trade-off between Reproductive and Ingestive Behavior.

Ingestive and sex behaviors are important for individual survival and reproductive success, but when environmental energy availability is limited, individuals of many different species make a trade-off, forfeiting sex for ingestive behavior. For example, food-deprived female Syrian hamsters (Mesocricetus auratus) forego vaginal scent marking and lordosis (sex behaviors) in favor of foraging, hoarding, and eating food (ingestive behavior). Reproductive processes tend to be energetically costly, and individual survival requires homeostasis in metabolic energy. Thus, during energetic challenges, the chances of survival are enhanced by decreasing the energy expended on reproductive processes. The entire hypothalamic-pituitary-gonadal (HPG) system is inhibited by severe energetic challenges, but comparatively little is known about the effects of mild energetic challenges. We hypothesized that (1) a trade-off is made between sex and ingestive behavior even when the level of food restriction is insufficient to inhibit the HPG system; (2) mild energetic challenges force a trade-off between appetitive ingestive and sex behaviors, but not consummatory versions of the same behaviors; and (3) the trade-off is orchestrated by ovarian steroid modulation of RFamide-related peptide 3 (RFRP-3). In other species, RFRP-3, an ortholog of avian gonadotropin-inhibitory hormone, is implicated in control of behavior in response to energetic challenges and stressful stimuli. In support of our three hypotheses, there is a "dose-response" effect of food restriction and re-feeding on the activation of RFRP-3-immunoreactive cells in the dorsomedial hypothalamus and on appetitive behaviors (food hoarding and sexual motivation), but not on consummatory behaviors (food intake and lordosis), with no significant effect on circulating levels of estradiol or progesterone. The effect of food restriction on the activation of RFRP-3 cells is modulated at the time of estrus in gonadally-intact females and in ovariectomized females treated with progesterone alone or with estradiol plus progesterone. Intracerebral treatment with RFRP-3 results in significant decreases in sexual motivation and results in significant but small increases in food hoarding in hamsters fed ad libitum. These and other results are consistent with the idea that ovarian steroids and RFRP-3 are part of a system that orchestrates trade-offs in appetitive behaviors in environments where energy availability fluctuates.

Maternal Programming of Body Weight in Syrian Hamsters.

Maternal programming of offspring energy balance has been viewed as an adaptation in which the gestational environment prepares the offspring to thrive and reproduce in that same postnatal environment. Programming might have the opposite effect, however, when gestational and postnatal environments are mismatched. Gestational programming would represent a trade-off if the mother can maximize fitness in one possible energetic future but cannot maximize fitness in another. The vast majority of research concerns rats, mice, or sheep, and dams are typically food restricted by 30-70% of ad libitum intake resulting in low birth weight and adult obesity in offspring. Few previous studies have used a lower level of food restriction, and no experiments, to the best of our knowledge, were designed to determine whether the effects of gestational restriction have postgestational effects independent of the effects that occurred during gestation. In the present experiment, Syrian hamsters were either restricted to 90% of their ad libitum food intake or fed ad libitum during pregnancy. All litters were cross-fostered at birth and all were fed ad libitum during lactation. Half of the litters from ad libitum-fed pregnant dams were fostered to dams that had been food restricted during pregnancy and half of the litters from food-restricted pregnant dams were fostered to ad libitum-fed dams. The latter group allowed us to test the hypothesis that the effects of having a gestationally food-restricted mother affects offspring characteristics independent of the prenatal programming. First, we found significant increases in the postnatal body weight of the offspring of ad libitum-fed mothers fostered to food-restricted dams, supporting the hypothesis that the effects of gestational restriction carry over to postnatal maternal ability (e.g., milk yield, milk content, or parental behavior). Second, the carry-over effects of gestational food restriction on offspring postnatal body weight were significant in male but not female offspring. This occurred even though this group had significantly lower food intake than offspring of ad libitum-fed mothers with ad libitum-fed foster mothers. In addition, and contrary to expectation, gestational food restriction had no significant effect on adult baseline food hoarding or food hoarding in response to food restriction. These results suggest that even mild energetic challenges during gestation can have postgestational effects on maternal ability, and the effects on offspring are sex-specific.

Estrous cycle fluctuations in sex and ingestive behavior are accentuated by exercise or cold ambient temperatures.

This article is part of a Special Issue "Energy Balance". In female Syrian hamsters (Mesocricetus auratus), low circulating levels of ovarian steroids are associated with increased food hoarding and decreased sexual motivation, but these effects are exaggerated in food-restricted females. To determine whether cold ambient temperature has the same effects as food restriction, groups of hamsters were fed ad libitum while they were housed at either 5 °C or 22 °C, and then tested for behavior for 90 min on each day of the estrous cycle. In females housed at 22 °C, high levels of sexual motivation and low levels of food hoarding were seen every day of the estrous cycle. In females housed at 5 °C, high levels of sexual motivation were restricted to the periovulatory day. On the three nonestrous days, these females showed high levels of food hoarding, but not food intake. A separate cohort of females were provided with access to running wheels and housed at 22 °C. They showed high levels of sexual motivation restricted to the periovulatory day, similar to the pattern of sexual motivation seen in cold-housed females. Unlike cold-housed females, those with running wheels showed low levels of food hoarding and high levels of food intake. Food restriction, cold housing, and access to wheels had no significant effect on plasma estradiol or progesterone concentrations, but significantly decreased plasma leptin concentrations. All three energetic challenges unmask estrous cycle fluctuations in sexual motivation that are obscured in laboratory conditions, i.e., isolation in a small cage with an overabundance of food.

Our stolen figures: the interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance.

This article is part of a Special Issue "Energy Balance". The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother's experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits.

When do we eat? Ingestive behavior, survival, and reproductive success.

The neuroendocrinology of ingestive behavior is a topic central to human health, particularly in light of the prevalence of obesity, eating disorders, and diabetes. The study of food intake in laboratory rats and mice has yielded some useful hypotheses, but there are still many gaps in our knowledge. Ingestive behavior is more complex than the consummatory act of eating, and decisions about when and how much to eat usually take place in the context of potential mating partners, competitors, predators, and environmental fluctuations that are not present in the laboratory. We emphasize appetitive behaviors, actions that bring animals in contact with a goal object, precede consummatory behaviors, and provide a window into motivation. Appetitive ingestive behaviors are under the control of neural circuits and neuropeptide systems that control appetitive sex behaviors and differ from those that control consummatory ingestive behaviors. Decreases in the availability of oxidizable metabolic fuels enhance the stimulatory effects of peripheral hormones on appetitive ingestive behavior and the inhibitory effects on appetitive sex behavior, putting a new twist on the notion of leptin, insulin, and ghrelin "resistance." The ratio of hormone concentrations to the availability of oxidizable metabolic fuels may generate a critical signal that schedules conflicting behaviors, e.g., mate searching vs. foraging, food hoarding vs. courtship, and fat accumulation vs. parental care. In species representing every vertebrate taxa and even in some invertebrates, many putative "satiety" or "hunger" hormones function to schedule ingestive behavior in order to optimize reproductive success in environments where energy availability fluctuates.