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

Abstract

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.

RFRP3 increases food intake in a sex‐dependent manner in the seasonal hamster Phodopus sungorus

“…Studies have reported that daily food intake decreases during the peri‐ovulatory period as a result of higher levels of oestrogens 45,46 . Furthermore, a recent study reported that RFRP3 neuronal activity in female Syrian hamsters correlated with low circulating sex steroid levels and higher food hoarding during most of the oestrus cycle, except for the day of pro‐oestrus when oestrogens are higher and animals eat less 47 . Taken together, these studies indicate that mimicking higher RFRP3 neuronal activation and peptide release by an i.c.v.…”

Gonadotrophin‐inhibitory hormone and its mammalian orthologue RFamide‐related peptide‐3: Discovery and functional implications for reproduction and stress

“…In addition to the suppressive effects on sexual behaviour described above, GnIH/RFRP has also been found to modulate displays of aggression in white crown sparrows and Japanese quail, and is associated with aggression in mice . Additionally, RFRP/GnIH stimulates feeding or food hoarding in a variety of avian and mammalian species . This has led to the proposition that RFRP may act to balance reproductive and metabolic needs .…”

“…150 Additionally, RFRP/GnIH stimulates feeding or food hoarding in a variety of avian and mammalian species. 28,78,[151][152][153][154] This has led to the proposition that RFRP may act to balance reproductive and metabolic needs. 78,155,156 However, additional exploration of the effects of GnIH/RFRP-3 at specific neural loci remains necessary because micro-infusion experiments suggest that the effects of RFRP-3 on feeding may depend on the targeted region.…”

RFRP-3, the Mammalian Ortholog of GnIH, Is a Novel Modulator Involved in Food Intake and Glucose Homeostasis

“…Reproduction is highly sensitive to changes in the metabolic status and energy reserves of an organism, and adverse metabolic conditions are commonly associated with defective reproductive capacity (6). In this context, studies focusing on the reproductive functions of the RFRP-3 system have also noted a potential role for RFRP-3 in appetite regulation (7,8). Exogenous administration of GnIH/RFRP-3 was shown to potently stimulate food intake in chickens and rats (9,10).…”