Lisa A. Eckel

Chronic administration of OB protein decreases food intake by selectively reducing meal size in female rats.

The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.

Spontaneous meal patterns in female rats with and without access to running wheels

Rats display strong behavioral rhythms during the ovarian cycle. During estrus, food intake is minimal due to a decrease in meal size, and locomotor activity is maximal. To investigate how activity influences feeding patterns across the ovarian cycle, we used a computerized system to monitor spontaneous meal patterns in intact, cycling female rats with and without access to running wheels. We found that running wheel access decreased dark meal frequency, increased dark meal size, and increased 24-h water intake during each phase of the ovarian cycle. In contrast, body weight, 24-h food intake, and the ovarian rhythms of reduced food intake, meal size, and body weight during estrus were not affected by running wheel access. In particular, the reduction in food intake during estrus was due to a selective reduction in dark meal size, not dark meal frequency, and this occurred independent of wheel access. These data indicate that estrus-related changes in spontaneous meal patterns and locomotor activity are independently controlled and that the reduction in food intake during estrus involves a selective change in the neurobiological controls of meal size.

Salivary cortisol in response to acute social rejection and acceptance by peers

Past research indicates that social rejection predicts a wide range of psychological problems (e.g., depression), but laboratory studies examining self-reports of negative affect after social rejection have reported inconsistent results. Salivary cortisol was measured before and after a social rejection/acceptance manipulation for objective assessment of psychological distress subsequent to peer rejection. Rejected participants were predicted to show significantly greater salivary cortisol than accepted or control participants. The present research also examined several factors that may moderate the relationship between acute rejection and cortisol. As predicted, rejected participants exhibited significantly higher cortisol than accepted or control participants. Defensiveness moderated the relationship between rejection and cortisol; highly defensive rejected participants showed significantly lower cortisol than less defensive rejected participants after peer rejection. Results indicate that social rejection causes psychological distress, but highly defensive individuals appear to be less susceptible than less defensive individuals to increases in salivary cortisol after acute social rejection.

Estradiol: a rhythmic, inhibitory, indirect control of meal size.

The classic analyses of the inhibitory effects of cholecystokinin (CCK) on meal size, conducted by Professor Gerard P. Smith and his colleagues at the Bourne Laboratory, inspired my initial interest in this field. My current research, which investigates the role of estradiol in the control of meal size, continues to be guided by Gerrys thoughtful, scientific approach to the study of ingestive behavior. In 1996, the year I arrived as a Postdoctoral Fellow at the Bourne Laboratory, Gerry published a new theory of the controls of meal size. In this important paper, Gerry proposed that the controls of meal size can be either direct or indirect. He argued that direct controls of meal size interact with peripheral, preabsorptive receptors that are sensitive to the chemical, mechanical, and colligative properties of ingested food and that indirect controls of meal size function to modulate the activity of direct controls. The purpose of this review is to illustrate how Gerrys theory has guided much of what is known about the mechanism by which estradiol inhibits food intake in female rats. I will provide evidence, primarily from behavioral studies of gonadally intact and ovariectomized rats, that estradiol exerts phasic and tonic inhibitory effects on food intake by acting as a rhythmic, inhibitory, indirect control of meal size.

Endogenous cholecystokinin’s satiating action increases during estrus in female rats

Food intake and meal size are reduced in female Long-Evans rats during estrus. To investigate the contribution of the satiating action of endogenous cholecystokinin (CCK) to this, rats were injected with 1 mg/kg of the potent, selective CCK(A) receptor antagonist, devazepide, during diestrus, when meal size is maximal, and during estrus, when it is minimal. Devazepide increased spontaneous food intake and meal size during estrus, but not during diestrus. Meal frequency was not affected by devazepide treatment. These results indicate that the potency of the CCK satiety-signaling system increases during estrus.

Gender differences in the association between psychopathic personality traits and cortisol response to induced stress.

Blunted stress reactivity has been implicated in the development of psychopathic personality traits. Cortisol is a biological marker of stress reactivity that has received little attention in prior psychopathy studies. The current investigation proposed that inhibition of cortisol response to induced stress is a reliable marker for psychopathic personality traits. An extreme groups methodology was used to recruit a mixed-gender sample of 84 college students characterized by high and low scores on the Levenson Self-Report Psychopathy Scale. Participants provided saliva samples prior to and after a well-established stress induction procedure (i.e., Trier Social Stress Test). These samples were assessed for cortisol (microg/dL) using an enzyme immunoassay procedure. Consistent with prediction, male participants high in psychopathic personality traits lacked stress induced increases in cortisol displayed by males low in psychopathic personality traits. This effect was not present in female participants. These findings suggest that cortisol production is a gender-specific marker for psychopathic personality traits.

Development of, and recovery from, activity-based anorexia in female rats.

Activity-based anorexia occurs in rats maintained on a restricted-feeding schedule while given free access to running wheels. These conditions induce high levels of wheel running and rapid weight loss. Although this procedure was developed as an animal model of anorexia nervosa, it has been studied primarily in male rats. Our goal was to examine the development of, and recovery from, activity-based anorexia in female rats. Food intake, wheel running, body weight, and phase of the estrous cycle were monitored daily prior to, during, and after a period of restricted feeding in which access to food was limited to 2 h/day. Food intake, body weight, and estrous cyclicity were also monitored in a control group housed without access to running wheels. Prior to food restriction, rats with wheels displayed high levels of wheel running and consumed more food than rats without wheels. Despite that both groups consumed similar amounts of food during the restricted-feeding phase, only rats with wheels developed symptoms of activity-based anorexia, including increased wheel running, rapid weight loss, and disruptions in estrous cyclicity. Recovery from activity-based anorexia was associated with hypoactivity and hyperphagia. Resumption of estrous cycles occurred when the weight lost during food restriction was regained. Hyperphagia, but not hypoactivity, was maintained following resumption of estrous cycles; however, this hyperphagia was limited to nonestrous phases. Our findings suggest that recovery from activity-based anorexia is mediated primarily by an increase in orexigenic signaling that promotes pronounced hyperphagia, and that the increase in satiogenic signaling during estrus abolishes this compensatory hyperphagia.

Submitting to Defeat Social Anxiety, Dominance Threat, and Decrements in Testosterone

Although theory suggests a link between social anxiety and social dominance, direct empirical evidence for this link is limited. The present experiment tested the hypothesis that socially anxious individuals, particularly men, would respond to a social-dominance threat by exhibiting decrements in their testosterone levels, an endocrinological change that typically reflects pronounced social submission in humans and other animals. Participants were randomly assigned to either win or lose a rigged face-to-face competition with a confederate. Although no zero-order relationship between social anxiety and level of testosterone was observed, testosterone levels showed a pronounced drop among socially anxious men who lost the competition. No significant changes were observed in nonanxious men or in women. This research provides novel insight into the nature and consequences of social anxiety, and also illustrates the utility of integrating social psychological theory with endocrinological approaches to psychological science.

The ovarian hormone estradiol plays a crucial role in the control of food intake in females

Despite a strong male bias in both basic and clinical research, it is becoming increasingly accepted that the ovarian hormone estradiol plays an important role in the control of food intake in females. Estradiols feeding inhibitory effect occurs in a variety of species, including women, but the underlying mechanism has been studied most extensively in rats and mice. Accordingly, much of the data reviewed here is derived from the rodent literature. Adult female rats display a robust decrease in food intake during estrus and ovariectomy promotes hyperphagia and weight gain, both of which can be prevented by a physiological regimen of estradiol treatment. Behavioral analyses have demonstrated that the feeding inhibitory effect of estradiol is mediated entirely by a decrease in meal size. In rats, estradiol appears to exert this action indirectly via interactions with peptide and neurotransmitter systems implicated in the direct control of meal size. Here, I summarize research examining the neurobiological mechanism underlying estradiols anorexigenic effect. Central estrogen receptors (ERs) have been implicated and activation of one ER subtype in particular, ERα, appears both sufficient and necessary for the estrogenic control of food intake. Future studies are necessary to identify the critical brain areas and intracellular signaling pathways responsible for estradiols anorexigenic effect. A clearer understanding of the estrogenic control of food intake is prerequisite to elucidating the biological factors that contribute to obesity and eating disorders, both of which are more prevalent in women, compared to men.

Estradiol decreases the orexigenic effect of neuropeptide Y, but not agouti-related protein, in ovariectomized rats.

Available data suggest that estradiol exerts an inhibitory effect on food intake by modulating the actions of multiple gut- and brain-derived peptides implicated in the control of food intake. For example, recent studies have shown that estradiol decreases the orexigenic effects of ghrelin and melanin-concentrating hormone. In the present study, we examined estradiols ability to decrease the actions of two additional orexigenic peptides, neuropeptide Y (NPY) and agouti-related protein (AgRP). Food intake was monitored following lateral ventricular infusions of 5 microg NPY, 10 microg AgRP, or saline vehicle in ovariectomized rats treated with either 1 microg estradiol or sesame oil vehicle. NPY increased food intake for 2h in both oil- and estradiol-treated ovariectomized rats. During this interval, the orexigenic effect of NPY was significantly greater in oil-treated rats, relative to estradiol-treated rats. In contrast to the short-term action of NPY, a single injection of AgRP increased food intake for 3 days in oil- and estradiol-treated rats. Meal pattern analysis revealed that the orexigenic effect of AgRP is mediated by an increase in meal size, not meal number. Unlike that observed following NPY treatment, estradiol failed to modulate the magnitude by which AgRP increased food intake and meal size. We conclude that a physiological regimen of estradiol treatment decreases the orexigenic effect of NPY, but not AgRP, in ovariectomized rats.