Food Intake In Female Rats Research Articles

The impact of binge-like palatable food intake on the endogenous glucagon-like peptide-1 system in female rats

Binge eating involves consumption of large amounts of food and a loss of control over the amount consumed. The incidence of binge eating disorder is higher in females than males, hinting at important sex differences in binge eating behavior, but the neural underpinnings of binge eating still remain unresolved. Recent work in male rats has shown that a history of binge-like palatable food intake suppresses hindbrain expression of preproglucagon (PPG), the precursor for glucagon-like peptide-1 (GLP-1). Given the roles of GLP-1 in reducing feeding and food reward, this could be a mechanism underlying binge-like eating in rodents. However, whether similar effects occur in female rats is unknown. Here, we tested the hypothesis that a history of binge-like palatable food intake in female rats would reduce PPG expression in the nucleus tractus solitarius (NTS), a key central site of GLP-1 production. Female rats given access to vegetable shortening every fourth day (4D) engaged in binge-like feeding, demonstrated by consuming significantly more shortening during the first hour of fat access compared to counterparts with ad libitum (AL) fat access. After several weeks of fat access under these schedules, PPG and GLP-1 receptor (GLP-1R) expression were measured in the NTS and ileum. Surprisingly, and in contrast to previous findings in male rats, there were no significant differences in expression of PPG or GLP-1R in either site in 4D versus AL rats, nor were there effects on plasma GLP-1 levels. These findings highlight key differences in the effects of binge-like intake on the central GLP-1 system in female compared to male rats.

Aerobic exercise attenuates the effects of ovariectomy and sedentarism on body composition and food intake in female rats

ABSTRACT Objective To evaluate the impact of low to moderate aerobic exercise and ovariectomy on body composition and food consumption in female rats. Methods Forty adult Wistar female rats (age: 23 weeks; body weight: 275.2±3.6g; mean±SEM) were divided into 4 groups (n=10): laparotomy-sedentary; laparotomy-exercised; ovariectomy-sedentary; and ovariectomy-exercised. The exercised groups were submitted to a treadmill running program (16m/min; 30min/day, 5 days/week), for 8 weeks. Body weight and food consumption were monitored during the experiment. Visceral fat and carcass water, protein, ash, fat and carbohydrate fractions were analyzed. Two-way ANOVA plus the Tukey’s post hoc test was used for comparisons and p<0.05 was considered significant. Results The ovariectomized (ovariectomy-sedentary+ovariectomy-exercised) and sedentary (laparotomy-sedentary+ovariectomy-sedentary) animals showed higher (p<0.05) weight gain, food consumption, food efficiency ratio and weight gain/body weight ratio than laparotomy animals (laparotomy-sedentary+laparotomy-exercised) and exercised (exercised laparotomy+exercised ovariectomy), respectively. The ovariectomized and sedentary animals showed higher (p<0.05) carcass weight, fat percentage and visceral fat than laparotomy and exercised rats, respectively. Conclusion Ovariectomy and physical inactivity increase obesogenic indicators, whereas regular aerobic exercise of low to moderate intensity attenuates these unfavorable effects in female rats.

The novel cannabinoid CB1 receptor agonist AM11101 increases food intake in female rats.

Δ9 -tetrahydrocannabinol (THC) acts via cannabinoid CB1 receptors to increase feeding. Here, we assessed the orexigenic effect of AM11101, a novel CB1 receptor agonist designed to have a more favourable pharmacodynamic profile than THC. The acute, orexigenic effects of AM11101 and THC were compared in female rats. Food intake and meal patterns were also examined following once daily treatment with AM11101 and THC for 7days. AM11101 (0.01-0.1mg·kg-1 ) increased food intake during the first hour following both acute and chronic treatments in pre-fed and freely feeding animals. This orexigenic effect persisted for up to 4hr, with no compensatory decrease in feeding during the subsequent 4-22hr. THC (1mg·kg-1 ) increased 1-hr food intake in pre-fed animals, but was less reliable than AM11101 in increasing 1-hr food intake in freely feeding animals following both acute and chronic administration. The orexigenic effect of both compounds was due to an increase in meal size, not meal number. Our study provides the first demonstration that AM11101 increases short-term food intake via a selective increase in meal size. AM11101 promotes a more reliable orexigenic effect than THC in freely feeding animals, with no subsequent compensatory decrease in feeding. AM11101 may offer a greater efficacy than THC and its congeners in stimulating food intake in underweight clinical populations.

Dietary daidzein induces accumulation of S-equol in enterohepatic circulation to far higher levels than that of daidzein in female rats with and without ovariectomy.

We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine distributions of daidzein and S-equol, a metabolite of intestinal bacterial conversion from daidzein, in the body. In the present study, we measured the concentrations of daidzein and S-equol in serum and bile in sham-operated and ovariectomized female rats fed a diet containing 150 mg/kg daidzein for 7 days. Dietary daidzein increased serum and bile concentrations of S-equol to far higher levels than those of daidzein. S-equol concentration was more than several hundred fold-higher in bile than in serum, regardless of ovariectomy. Moreover, to investigate whether accumulation of S-equol is facilitated by efficient enterohepatic circulation during continuous intake of daidzein and S-equol, female rats were fed diet containing daidzein or S-equol (both 150 mg/kg), or control diet for 1, 2, 3, or 5 days. Dietary daidzein significantly increased serum and bile concentrations of S-equol in a time-dependent manner, but not those of daidzein. These results indicated that substantial proportion of dietary daidzein was converted to S-equol, which underwent efficient enterohepatic circulation and predominantly accumulated there.

The effects of relaxin-3 knock down neurons on body weight and food intake in female rats

The effects of relaxin-3 knock down neurons on body weight and food intake in female rats

Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats

Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0–200 μg/kg), a GPER-1 agonist (G-1; 0–1600 μg/kg), and a GPER-1 antagonist (G-36; 0–80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect.

Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female Rats.

Comfort eating during periods of stress is a common phenomenon observed in both animals and humans. However, the underlying mechanisms of stress‐induced food intake remain elusive. The amygdala plays a central role in higher‐order emotional processing and the posterodorsal subnucleus of the medial amygdala (MePD), in particular, is involved in food intake. Extra‐hypothalamic corticotrophin‐releasing factor (CRF) is well recognised for mediating behavioural responses to stress. To explore the possible role of amygdala CRF receptor activation in stress‐induced food intake, we evaluated whether a stressor such as tail‐pinch, which reliably induces food intake, would fail to do so in animals bearing bilateral neurotoxic lesions of the MePD. Our results showed that ibotenic acid induced lesions of the MePD markedly reduced tail‐pinch induced food intake in ovariectomised, 17β‐oestradiol replaced rats. In addition, intra‐MePD (right side only) administration of CRF (0.002 or 0.02 ng) via chronically implanted cannulae resulted in a dose‐dependent increase in food intake, although higher doses of 0.2 and 2 ng CRF had less effect, producing a bell shaped curve. Furthermore, intra‐MePD (bilateral) administration of the CRF receptor antagonist, astressin (0.3 μg per side) effectively blocked tail‐pinch induced food intake. These data suggest that the MePD is involved in stress‐induced food intake and that the amygdala CRF system may be a mediator of comfort eating.

Dynamics of appetite-mediated gene expression in daidzein-fed female rats in the meal-feeding method.

We previously found that daidzein decreased food intake in female rats. The present study aimed to elucidate the relationship between dynamics of appetite-mediated neuropeptides and the anorectic effect of daidzein. We examined appetite-mediated gene expression in the hypothalamus and small intestine during the 3 meals per day feeding method. Daidzein had an anorectic effect specifically at the second feeding. Neuropeptide-Y (NPY) and galanin mRNA levels in the hypothalamus were significantly higher after feeding in the control but not in the daidzein group, suggesting that daidzein attenuated the postprandial increase in NPY and galanin expression. The daidzein group had higher corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamus after feeding, and increased cholelcystokinin (CCK) mRNA levels in the small intestine, suggesting that CCK is involved in the hypothalamic regulation of this anorectic effect. Therefore, daidzein may induce anorexia by suppressing expression of NPY and galanin and increasing expression of CRH in the hypothalamus.

Effect of tributyltin on the food intake and brain neuropeptide expression in rats.

Tributyltin (TBT) is a largely diffused environmental pollutant. Several studies have demonstrated that TBT is involved in the development of obesity. However, few studies addressing the effects of TBT on the brain neuropeptides involved in appetite and body weight homeostasis have been published. Experiments were carried out on female and male Sprague-Dawley rats. Animals were exposed to TBT (0.5 μg/kg body weight) for 54 days. The hepatic triglyceride and total cholesterol were determined using commercial enzyme kits. The NPY, AgRP, POMC and CART mRNA expression in brains were quantified by real-time PCR. TBT exposure resulted in significant increases in the hepatic total cholesterol and triglyceride concentration of both male and female rats. Interestingly, increases in body weight and fat mass were only found in the TBT-treated male rats. TBT exposure also led to a significant increase in food intake by the female rats, while no change was observed in the male rats. Moreover, the neuropeptides expression was different between males and females after TBT exposure. TBT induced brain NPY expression in the female rats, and depressed brain POMC, AgRP and CART expression in the males. TBT can increase food intake in female rats, which is associated with the disturbance of NPY in brains. TBT had sex-different effects on brain NPY, AgRP, POMC and CART mRNA expression, which indicates a complex neuroendocrine mechanism of TBT.

A2A adenosine receptor agonists reduce both high-palatability and low-palatability food intake in female rats

The present study examined the effect of two A(2A) adenosine receptor (AR) agonists, CGS 21680 and VT 7, on high-palatability food (HPF) intake in a model of binge eating in sated rats and on low-palatability food (LPF) intake in food-deprived rats. Binge eating was induced in female rats by three 8-day cycles of food restriction/refeeding, followed by acute stress. Two groups of rats were used: NR+NS rats normally fed and not stressed and R+S rats exposed to cycles of food restriction/refeeding and then stressed. R+S rats had higher intake of HPF than the NR+NS controls. The two A(2A)AR agonists were tested at doses of 0.1 and 0.05 mg/kg intraperitoneally; VT 7 did not modify locomotor activity at either dose, whereas CGS 21680 only slightly reduced it at the higher dose tested. The injection of 0.1 mg/kg of both agonists markedly reduced HPF intake both in R+S and in NR+NS rats. The dose of 0.05 mg/kg was inactive. CGS 21680 and VT 7, 0.1 mg/kg, also reduced the standard LPF intake in 24 h food-deprived rats; however, they did not reduce water intake, indicating that their effect on food intake is selective. The dose of 0.05 mg/kg was inactive. Thus, A(2A)AR agonists exert a rather general effect on food intake, inhibiting both HPF intake in sated rats and LPF intake in food-deprived rats. They may potentially be useful pharmacological agents to control binge-related eating disorders and to reduce food overconsumption associated with obesity.

Sex hormones differentially influence voluntary running activity, food intake and body weight in aging female and male rats

The aim of this study was to examine the longer-term effects of reduced gonadal hormones on food intake, food efficiency, voluntary running activity and body weight in mature male and female rats, compared to age-matched controls. We hypothesized that hormonal effects would differ for rats that were not rapidly growing and our results are consistent with this hypothesis. 6-8month male and female rats were divided into four groups: Female and male control groups and a female and male experimental group. Control groups were intact for 46weeks. Experimental groups were intact during Phase I (16weeks), ovariectomized or orchidectomized during Phase II (20weeks), and received estrogen or testosterone hormone replacement therapy (HRT) during the final Phase III (10weeks). Food intake and running distance were monitored daily and body weight was recorded weekly for 46weeks. Contrary to findings for young and growing animals, we did not observe a (1) stabilization of food intake in female rats following OVX, (2) loss of body weight with ORX in males, or (3) complete restoration of running activity in ORX males given testosterone, compared to females given estrogen. Feeding efficiency was not affected by aging in females or males. Loss of estrogen increased energy intake whereas reduced testosterone in males resulted in a negative energy balance. Findings suggest variable hormonal effects for aging male/female rats.

Leptin-derived peptides that stimulate food intake and increase body weight following peripheral administration

We previously showed that peptides containing leptin sequences 1–33 or 61–90 are taken up by the rat brain. We now report the effects of these peptides on food intake and body weight in mature rats. Peptides were infused intravenously for 4 weeks, using Alzet minipumps. Dosages were 20 μg/kg/day in experiment I, and 60 μg/kg/day in experiment 2. In experiment 1, female rats receiving peptides 1–33 and 61–90 each underwent an approximate doubling of the weight gain of control rats. These peptides also increased food intake in female rats. Peptide 15–32, which has a lesser degree of brain uptake, gave a smaller weight gain. Peptide 83–108, which is not taken up by the brain, had no effect on weight gain or food intake. Similar results were obtained in experiment 2. In male rats, however, none of the peptides caused significant changes in food intake or body weight. This was at least partly due to the fact that all male rats underwent vigorous weight increases. We conclude that peptides 1–33 and 61–90 acted as leptin antagonists, stimulating food intake and body weight increases, at least in female rats. These peptides may lead to clinical applications in conditions such as anorexia and cachexia.

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. Estradiol's 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 estradiol's 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 estradiol's 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.

Activation of ERα is necessary for estradiol's anorexigenic effect in female rats

While there is considerable evidence that the ovarian hormone estradiol reduces food intake in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. While several studies have demonstrated that activation of ERα, but not ERβ, is sufficient to reduce food intake in ovariectomized (OVX) rats, there are limited data regarding which receptor subtype is necessary. Here we used the selective ERα and ERß antagonists, MPrP and PHTPP, respectively, to investigate this question. We found that antagonism of ERα, but not ERβ, prevented the decrease in food intake following acute administration of estradiol in OVX rats. In addition, antagonism of ERα prevented the estrous-related, phasic reduction in food intake that occurs in response to the rise in circulating levels of estradiol in cycling rats. We conclude that activation of ERα is necessary for the anorexigenic effects of exogenous and endogenous estradiol in female rats.

Adaptation of Feeding and Counter‐Regulatory Hormone Responses to Intermediate Insulin‐Induced Hypoglycaemia in the Ovariectomised Female Rat: Effects of Oestradiol

Oestradiol regulates basal food intake and glucagon and corticosterone secretion, but its influence on these responses to acute and recurring hypoglycaemia remains unclear. The present study utilised an experimental model for repeated intermediate-acting insulin-induced hypoglycaemia that replicates the route of delivery, frequency of administration, and duration of insulin action in the clinical setting. Groups of ovariectomised (OVX) rats were implanted with s.c. capsules containing oestradiol benzoate (EB) or oil, and injected with one or four doses of Humulin neutral protamine Hagedorn (HN), on as many days, or diluent alone. Baseline feeding followed divergent trends in EB- versus oil-implanted animals over a 9-h period after final injections. Recurring HN-induced hypoglycaemia resulted in significantly greater baseline-corrected food intake in OVX + EB and OVX + oil groups, relative to acute hypoglycaemic hyperphagia. Although oestradiol did not modify net food consumption after single or serial HN doses, EB replacement maintained uniform feeding over time in each treatment paradigm. Baseline glucagon and corticosterone secretion was higher in EB- versus oil-treated OVX rats. Oestradiol prolonged acute hypoglycaemic glucagonemia, and increased the magnitude, but shortened the duration, of glucagon secretion during recurring hypoglycaemia. OVX + oil rats responded to both acute and recurring hypoglycaemia with elevated corticosterone secretion at a single time point, which was advanced from +6 to +4 h during recurrent insulin-induced hypoglycemia, whereas OVX + EB animals exhibited increased plasma hormone levels at both +4 and +6 h in response to each paradigm. Area-under-the curve analyses showed that total glucagon and corticosterone release was greater in EB- versus oil-implanted rats after both single and serial dosing with HN. These results demonstrate that repeated HN administration increases food intake in female rats via oestrogen-independent mechanisms, but that oestradiol preserves temporal patterns of hypoglycaemic hyperphagia. The data also reveal that normo- and hypoglyacemic glucagon and corticosterone secretion are enhanced in the presence of oestrogen. Further studies are necessary to identify the sites and cellular substrates that are responsible for this hormonal regulation of behavioural and endocrine responses to prolonged hypoglycaemia.

Influence of ovarian hormones on development of ingestive responding to alterations in fatty acid oxidation in female rats

Adult male rats have been demonstrated to increase food intake in response to administration of drugs that interfere with oxidation of fatty acids (e.g. methyl palmoxirate and mercaptoacetate [MA]), effects that are larger in animals maintained on a high-fat diet. In contrast, while administration of MA has been reported to stimulate food intake in pre-pubertal female rats, food intake is not stimulated by MA in adult female rats. Instead, administration of MA to adult females results in changes in reproductive behavior and physiology. The present experiments were designed to examine the effects of administration of MA on food intake in adult female rats. The results demonstrated that, as previously reported, food intake was stimulated by MA in adult male rats on low-fat and high-fat diets, but food intake was not stimulated by MA in gonadally-intact adult female rats on either low-fat or high-fat diet. Further, MA did not stimulate food intake in female rats ovariectomized as adults. However, when females were ovariectomized prior to the onset of puberty (postnatal day 25–28), food intake was stimulated by administration of MA in adulthood. Finally, cyclic injections of 17-β-estradiol benzoate given to females ovariectomized prior to the onset of puberty abolished the stimulatory effects of MA on food intake in adult females. Taken together, the data suggest that exposure to estrogens during the time of puberty in female rats can persistently alter adult ingestive responding to signals related to changes in energy utilization.

Dietary Soy Isoflavone–Aglycone Lowers Food Intake in Female Rats With and Without Ovariectomy

Estrogens downregulate eating behavior, and soy isoflavones are known to be estrogenic agents. We aimed to examine whether the estrogenic property of soy isoflavones can affect food intake and body weight. Seven-week-old male, female, and ovariectomized (OVX) Sprague-Dawley rats were given free access to a diet containing 100-300 mg total isoflavone/kg diet, or to a control diet, either with or without concurrent administration of estradiol by subcutaneous implantation. Dietary soy isoflavone was shown to lower food intake in female rats, whether or not the animals had undergone ovariectomy. Administration of estradiol lowered the food intake in male rats and in OVX female rats. The decrease in weekly food intake in female rats led to a reduction in their weekly gain in body weight. Dietary soy isoflavone significantly increased the concentration of serum isoflavones, especially equol (a metabolite of daidzein), regardless of gender or ovariectomy. Dietary soy isoflavone did not affect either serum estradiol concentration or uterine and didymus weights, but estradiol administration improved the uterine atrophy in OVX rats, and decreased the didymus weight in male rats. Soy isoflavone lowers the food intake in female rats, but not in the male animals. Contrary to the hypothesis currently in vogue, the reduction in food intake caused by soy isoflavone may not be a purely estrogenic effect. This follows from the finding that the effects of soy isoflavones on food intake and on the reproductive organs differ from the corresponding effects produced by estrogen.

A re-examination of septal lesion-induced weight gain in female rats

A re-examination of septal lesion-induced weight gain in female rats. PHYSIOL BEHAV Previous studies that examined the effects of knife cuts ventral to the septal area, or the pattern of anterograde degeneration after other obesity-inducing lesions or cuts, have implicated the septal area in feeding behavior. However, lesion studies have been inconsistent. In the present study, large electrolytic lesions that destroyed all or nearly all of the septal area resulted in excessive weight gain in female rats (25 g/20 days compared to 1 g/20 days for controls). Lesions confined to the ventral septum produced equal weight gains, but rats with lesions confined to the dorsal septum did not differ from controls. The excessive weight gains were accompanied by modest hyperphagia. The weight gains were not the result of incidental damage to adjacent structures such as the stria terminalis or the shell of the nucleus accumbens. It is concluded that the ventral portion of the septum is part of a limbic-hypothalamic circuitry regulating food intake in female rats.

Acute Lipoprivation Suppresses Pulsatile Luteinizing Hormone Secretion without Affecting Food Intake in Female Rats

The present study examined the effect of acute lipoprivation on pulsatile luteinizing hormone (LH) secretion in both normal-fat diet, ad libitum-fed and fasted female rats. To produce an acute lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acid oxidation, was administered intraperitoneally to ad libitum-fed or 24-h fasted ovariectomized (OVX) rats with or without an estradiol (E2) implant, that produces a negative feedback effect on LH pulses. The steroid treatment was performed to determine the effect of estrogen on lipoprivic changes in LH release, because estrogen enhances fasting- or glucoprivation-induced suppression of LH pulses. Pulsatile LH secretion was suppressed by MA administration in a dose-dependent manner in the ad libitum-fed OVX and OVX+E2 rats. LH pulses were more severely suppressed in the 24-h-fasted OVX and OVX+E2 rats compared to the ad libitum-fed rats. Estrogen slightly enhanced lipoprivic suppression but the effect was not significant. In the present study, increased plasma glucose and free-fatty acid concentrations may indicate a blockade of fatty acid metabolism by the MA treatment, but food intake was not affected by any of the MA doses. Acute vagotomy did not block lipoprivic suppression of LH pulses. Thus, the present study indicates that lipid metabolism is important for maintenance of normal reproductive function even in rats fed a normal-fat diet and lipoprivation may be more critical in fasted animals that probably rely more heavily on fatty acid oxidation to maintain appropriate metabolic fuel levels. In addition, failure of blockade of lipoprivic LH inhibition by vagotomy suggests that lipoprivic information resulting in LH suppression is not transmitted to the brain via the vagus nerve.

Meal patterns in female rats during and after intermittent nicotine administration

Previously we observed in male rats that intermittent administration of nicotine (NIC) during the dark phase reduces food intake (FI) by initially decreasing only dark phase meal size. This was followed several days later by an increase in dark phase meal frequency such that FI returned to normal, while body weight remained suppressed. Termination of NIC treatment resulted in a modest dark phase hyperphagia. Since some human females use NIC as a weight control drug, the present study investigated changes in FI and body weight regulation in adult female rats treated for five estrous cycles with saline or a 1.40 mg/kg/day (free base) dose of NIC, which was given in four equal i.p. doses during the dark phase. The rats were followed for 15 days after cessation of NIC. Initially both dark and light phase FI were reduced and this was caused by an immediate decrease in dark and light phase meal size; the attenuation of meal size continued after cessation of NIC. On day 7 of NIC, the rats compensated by significantly increasing the number of dark, but not light, phase meals they took. This resulted in a normal 24-h FI, which was caused by a dark phase increase in FI coupled with a continued decrease in light phase FI. Importantly, these changes in meal patterns persisted for some time after termination of NIC. Upon NIC cessation, the NIC group showed no hyperphagia even though their body weight was significantly decreased. These results document that administration of NIC during the dark phase resulted in a reorganization of the microstructure of FI in females rats that resembles, but does not exactly duplicate, that observed in male rats. Like males, long lasting alterations in the microstructure of FI (e.g., meal size and meal number), were noted in female rats for up to 2 weeks after cessation of NIC. These results differ from studies in which NIC was given continuously 24-h per day and indicate that dark phase NIC administration in rats may represent an appropriate model to study the impact of NIC on meal patterns.