Sensitization of food reinforcement is related to weight status and baseline food reinforcement.

BACKGROUND: Food reinforcement is an empirical index of motivation to obtain food. Higher levels of food reinforcement are associated with increased energy intake and increased body weight. Food reinforcement can vary over repeated food presentations, as people may show reduced reinforcing value if they satiate to repeated reinforcers, or they may show sensitization, or an increase in reinforcing value with repeated presentations. Over the past few years, our laboratory has been studying the impact of repeated administration of large portions of high energy density snack foods on food reinforcement. We have shown in three separate studies that the majority of non-obese individuals become satiated after 2 weeks of the same snack food administration, but that a subset of obese individuals sensitize after this same manipulation. OBJECTIVE: The purpose of the study presented here was to identify predictors of reinforcer satiation or sensitization. SUBJECTS: For the analyses presented here, we combined data sets from three previous studies for a total of 67 adult participants. RESULTS: We found that higher body mass index (BMI) and higher baseline motivation to eat predicted sensitization, and baseline motivation to eat moderated the effects of BMI, such that higher baseline responding for food predicted sensitization in obese individuals, but satiation in non-obese individuals. CONCLUSIONS: These data suggest that repeated exposure to high energy density snack foods may result in sensitization to those foods, with similar effects as drugs of abuse in susceptible individuals, and that an individual's BMI and baseline responding act as predictors of this response.

Relationship between sex of parent and child on weight loss and maintenance in a family-based obesity treatment program.

OBJECTIVE: To determine if the sex of the participating parent/child pair is a contributing factor in initial weight loss and maintenance within a family-based obesity treatment program. DESIGN: A 2-year family-based obesity treatment program targeting one overweight parent and one overweight child. SUBJECTS: One overweight parent (body mass index (BMI) > or = 25) and child (> or = 85th BMI percentile) from 164 families. MEASUREMENTS: Parameters of body weight, including height, weight, BMI, z-BMI, percent overweight (BOV) at baseline and at 6-, 12- and 24-month follow-up time points. RESULTS: Children within the opposite-sex dyads had greater weight loss (P < 0.01) at 6- and 12-month time points compared with children in the same-sex dyads. Parents within opposite-sex dyads had significantly greater weight loss at 24 months (P < 0.05) compared with those in the same-sex dyads. When individual dyads were examined, the change in child z-BMI after 6 months was greater for the mother-son dyad as compared to the mother-daughter and father-son (P < 0.05). For parent z-BMI, the mother-daughter dyad consistently exhibited the poorest results. At 6- and 12-month time points, parents in the mother-daughter dyad lost significantly less weight than parents in all other dyads (P < 0.05), and at 24 months, parents in the mother-daughter dyad lost less weight than parents in the opposite-sex dyads (P < 0.05). CONCLUSION: These data reveal that child-parent sex interactions can strongly influence the outcome of obesity treatment when both parent and child are the target for weight loss. The reasons that underlie this effect remain to be determined.

Developmental changes in GABA receptor subunit composition within the gonadotrophin-releasing hormone-1 neuronal system.

It is becoming increasingly evident that GABA plays an important role in the regulation of gonadotrophin-releasing hormone (GnRH)-1 neurones via the GABAA receptor. The aim of the present study was to characterise expression of the GABAA receptor within the GnRH-1 system across development. The expression pattern of five GABAAalpha subunits and one GABAAbeta subunit was first examined within individual GnRH-1 neurones by the polymerase chain reaction. A significant increase in the expression of GABAAalpha2 and a significant decrease in the expression of GABAAalpha6 over time were found. Of the other subunits examined, two (alpha1 and alpha3) showed no differences in expression and two (alpha4 and beta3) showed variable low incidence of expression. Given the reciprocal relationship of alpha2 and alpha6 expression, we hypothesised that there is a developmental switch in the expression of these subunits in GnRH-1 neurones. To investigate this hypothesis, single- and double-label immunocytochemistry for GABAAalpha2 and alpha6 and GnRH-1 was performed in tissue from ages E12.5 to adulthood, as well as in nasal explants. We show that GABAAalpha2 and alpha6 are present in the GnRH-1 neuronal system both in vivo and in vitro and that the levels of expression are altered as a function of age.

Glucocorticoids affect gonadotropin-releasing hormone immunoreactivity in musk shrew brain.

Multiple interactions between the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal systems exist. In this study, we asked if glucocorticoid administration affected gonadotropin-releasing hormone (GnRH) immunoreactivity. We found that musk shrews treated with dexamethasone (DEX), a synthetic glucocorticoid, had more GnRH-immunoreactive (ir) cells in the forebrain than did cortisol- or control-treated animals. The effects of DEX were noted rapidly, within 15 min, after administration. These effects were observed in the forebrain as a whole and also in specific subpopulations of GnRH-ir cells located in the medial septum/diagonal band and the hypothalamus.

Coumestrol antagonizes neuroendocrine actions of estrogen via the estrogen receptor alpha.

The phytoestrogen coumestrol has estrogenic actions on peripheral reproductive tissues. Yet in the brain this compound has both estrogenic and anti-estrogenic effects. We used estrogen receptor alpha knockout mice (ERalphaKO) to determine whether coumestrol has estrogenic actions in mice and also if these effects are mediated by the classic ERalpha. Female wild-type (WT) and ERalphaKO mice were ovariectomized and treated with estradiol (E2), dietary coumestrol, both, or neither compound. Ten days later the animals were sacrificed, blood was collected, and brain tissues were perfused. Fixed brains were sectioned and immunocytochemistry was employed to quantify progesterone receptors (PR) in the medial preoptic (POA) and ventromedial nucleus of the hypothalamus (VMN). Plasma was assayed for luteinizing hormone (LH). Estrogen treatment induced PR immunoreactivity in both regions in brains of WT females. In ERalphaKO mice, lower levels of PR were induced. The stimulatory effects of E2 on PR were attenuated in the POA by cotreatment with coumestrol, and the same trend was noted in the VMN. WT ovariectomized females treated with E2 had low levels of LH, while LH was high in untreated females and even higher in ovariectomized females treated with coumestrol. ERalphaKO females in all treatment groups had high levels of LH. Taken together, the results show that coumestrol has anti-estrogenic actions in the brain and pituitary and that ERalpha mediates these effects.

Estrogen receptor beta regulates sexually dimorphic neural responses to estradiol.

Estrogen receptors (ERs) mediate many sexual dimorphisms in the neuroendocrine system and in behavior. We examined the consequences of the loss of functional estrogen receptor beta (ERbeta) on two sexually differentiated neural responses to estrogen. In wild type (WT) male mice, but not in females, estradiol (E(2)) treatment decreased estrogen receptor alpha immunoreactive (ERalpha-ir) cell numbers in the arcuate nucleus (ARC), the preoptic area (POA), and the ventromedial nucleus (VMN). These sex differences were reversed in ERbeta knockout (ERbetaKO) mice. Castrated ERbetaKOs did not show any change in ERalpha-ir cell number after E(2) treatment. Yet, E(2) decreased ERalpha-ir cell number in ovariectomized ERbetaKOs. Estradiol treatment increased progesterone receptor immunoreactive (PR-ir) cell number in WT female VMN and POA, but no change was noted in brains of WT castrates. In ERbetaKO mice the opposite relationship was found, E(2) treatment increased PR-ir cell number in male, but not in female, brains. Our results show that ERbeta influences several sexually dimorphic neural responses to estrogen. Moreover the data clearly show that ERbeta can modulate neural expression of ERalpha.

Acute re-feeding reverses food restriction-induced hypothalamic-pituitary-gonadal axis deficits.

Undernutrition has well-established effects on female reproduction. Here we describe the effects of food restriction on aspects of the hypothalamic-pituitary-gonadal (HPG) axis in the female musk shrew. We determined that acute re-feeding reverses deficits brought on by food restriction. Two days of food restriction led to an increase in proGnRH immunoreactive cells in the preoptic area relative to ad libitum-fed controls (AL). This increase was reversed by 90 min of ad libitum feeding in the re-fed females (RF). In addition, food-restricted (FR) females had significantly greater GnRH content in the median eminence than either the AL or RF females. After GnRH was administered, the majority of females in all food conditions ovulated, yet the FR females had significantly fewer corpora lutea than either the AL or RF animals. These data show that food restriction impairs HPG axis function in female musk shrews, and that some of these impairments can be rapidly reversed by acute re-feeding.

Brief refeeding restores reproductive readiness in food-restricted female musk shrews (Suncus murinus).

Food deprivation blocks sexual behavior and disrupts estrous cycles in mammals. We asked whether reduced copulatory behavior, produced by limited food intake, could be reversed by brief refeeding intervals in the female musk shrew. In Experiment 1, animals were food restricted to 60% of ad lib (FR), and an additional group of FR females were refed for 90 min prior to testing (RF). Refed and ad lib (AL) fed females were significantly more likely to mate than FR females. To test the hypothesis that food-induced restoration of copulatory behavior is not the result of changes in peripheral steroids, we repeated Experiment 1 using ovariectomized and testosterone-implanted females. The results from Experiment 2 were similar to those found in the first study. Next, a more severe refeeding schedule was employed; females were restricted to 50% of ad lib intake. Females in the RF and FR groups were significantly less likely than the AL animals to mate. In the last experiment, females were food restricted to 50% and longer refeeding intervals were employed. Four and one-half hours of food intake did not reinstate sexual behavior, but females refed for 12 h were as likely to mate as ad lib fed controls. We also did not detect any differences in plasma concentrations of testosterone and cortisol in AL, FR, and RF ovary-intact animals. These results define a nutritional threshold for copulatory behavior in the musk shrew. Since this species is highly sensitive to small alterations in food intake, it is a useful model for studies of interactions between metabolic fuels and behavior.