A pharmacological analysis of food intake regulation in rats treated neonatally with monosodium L-glutamate (MSG)

Studies were conducted to examine deficits in food intake regulation in MSG-treated rats that result from known or suspected damage to neurotransmitter systems involved in feeding. Male rats were injected with either MSG (4 mg/g) or sodium chloride on postnatal days 2 and 4 (MSG-Lo) or postnatal days 2, 4, 6 and 8 (MSG-Hi). As adults, MSG-treated and control rats (n = 12/group) were examined for deficits in pharmacologically elicited feeding and other measures of food intake regulation. A second group of MSG-treated (n = 9/group) and control rats (n = 12) were used to measure basal blood pressure and nociceptive reactivity in adulthood. Organ weights, body weight and neuropeptide Y (NPY) content in brain regions were determined at the end of the study. MSG-Hi rats consumed significantly less food than controls during the dark part of the light cycle. Both MSG-Hi and MSG-Lo groups ate significantly less food than controls after a 48-hour fast. MSG-Hi and MSG-Lo rats consumed significantly less food than controls in response to 1.0 mg/kg morphine. MSG-Hi rats consumed significantly less food than controls during the dark phase and significantly more food than controls during the light phase in response to naloxone (1.0 mg/kg). MSG-Lo ate significantly more than controls in response to 0.1 mg/kg guanfacine. MSG-Hi and MSG-Lo showed a significant attenuation in diazepam-stimulated feeding when compared to controls. Blood pressure was significantly lower in both MSG-Hi and MSG-Lo rats compared to controls. Tail flick latencies were not altered by MSG-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of reserpine and stress on feeding behaviour in the light and dark phases of the diurnal cycle in rats

Abstract— The effect of reserpine (2·5 mg kg^?1 subcutaneously) and stress (3 h restraint) on food and water consumption and body weight change in the light and dark phases of the diurnal cycle in rats was investigated. Reserpine increased water intake and body weight loss in the light phase (250 and 180% of the control, respectively). In the dark phase the reserpinized rats consumed less food and water (20 and 30% of the control, respectively) and body weight gain was reversed (–250% of the control). After stress, rats consumed more food and water (200 and 500% of the control, respectively) and their body weight loss was diminished (60% of the control) in the light phase. In the dark phase the consumption of food and water in the stressed rats was diminished (80 and 85% of the control, respectively) without any change in body weight gain. The dark/light phase ratio for food consumption, water intake and body weight change (gain/loss) was highly statistically significant in the stressed and reserpine-treated rats. The results indicate that evaluation of behaviour in animal models should be carried out during both phases of the diurnal cycle.     

The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats

This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.     

An acute i.c.v. infusion of leptin has no effect on hypothalamic histamine and tele-methylhistamine contents in Wistar rats

The actions of intracerebroventricularly (i.c.v.) infused leptin on food intake, body weight and hypothalamic contents of histamine and tele-methylhistamine, the main histamine metabolite in the mammalian brain, were studied in male Wistar rats. The effect of the histamine H(1) receptor blockade on leptin-induced anorexia was also examined. It was found that leptin at the dose of 10 microg i.c.v. reduced 24-h food intake by 48% as compared with the controls (P<0.01). This leptin dose reduced feeding during 2-4 consecutive days. In spite of the marked changes in food consumption and body weight gain, leptin did not alter the hypothalamic contents of histamine and tele-methylhistamine. Furthermore, the blockade of histamine H(1) receptors by mepyramine did not attenuate the effect of leptin on feeding and body weight. The findings indicate that centrally administered leptin suppresses feeding and promotes weight loss through mechanisms that do not require the direct participation of the brain histaminergic neuron system.     

Chronic nicotine exposure in rat: A behavioural and biochemical study of tolerance

Rats received nicotine (50 mg nicotine base/1) in their drinking fluid for 28 days. The daily consumption of nicotine was about 4 mg/kg per day. Controls received plain water. Body weight, food consumption and fluid intake were registered during the whole treatment period and up to 31 days after withdrawal of nicotine. A significant lower body weight was noted in rats, treated with nicotine, in comparison with control rats during the whole treatment period. After withdrawal of nicotine the body weight returned to normal. Only slight effects were seen on the food intake (at the beginning of the nicotine treatment). The fluid intake, on the other hand, was significantly lower in the nicotine group during the whole period of treatment and a reduced intake persisted 28 days after withdrawal of nicotine.Tolerance to nicotine was measured in rats 24 hours after withdrawal of nicotine, using two behavioural tests. No tolerance to nicotine was found after 31 days of withdrawal of nicotine.The number of nicotine-like binding sites was found to be reduced in the midbrain 24 hours after withdrawal of nicotine, while no significant change was found in the cortex and hippocampus.     

Prenatal cocaine: maternal toxicity, fetal effects and locomotor activity in rat offspring

Either 30 or 60 mg/kg of cocaine hydrochloride (COC) was administered by gastric intubation to gravid rats during the last two weeks of gestation. A pair-fed control group was administered the vehicle alone and allowed to eat and drink only the amount consumed by the 60 mg/kg group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. None of the treated dams died nor were any gross signs of cocaine toxicity observed. Among the COC-60 dams, there was a reduction in food and water intake at the beginning of treatment; whereas water intake returned to control levels, food intake remained approximately 12% below that of the controls. Compared to the nontreated dams, both COC-treated and pair-fed dams gained significantly less body weight from conception to term. Cocaine had no effect on offspring mortality, birthweight or rate of postnatal growth. Measurement of the ontogeny of motor activity during the first month of life revealed a similar activity pattern for all the groups except for the COC-60 group which showed heightened activity on Days 20 and 23. These findings are discussed in relation to other animal and clinical reports of prenatal cocaine exposure.     

Evaluation of a Rat Model of Valproate-Induced Obesity

Long-term treatment with the anticonvulsant valproate (VPA) leads to well-documented weight gain and obesity in humans. In an attempt to develop an animal model of this condition, adult rats were given VPA 20 g/kg (high-dose) or 2 g/kg (low-dose) in their daily feeding or orally 120 mg/kg body weight/day in two divided doses, and food intake and body weight were assessed. Valproate resulted in lower body weights in all protocols. Food intake was lower (p<0.001) for rats receiving high-dose VPA than for controls. Feed efficiency (change in weight divided by cumulative food intake for that period) was lower than that of controls for both high (p<0.0001) and low doses (NS). Metabolic rate and physical activity were not different between control and VPA animals, although decreased food intake would be expected to decrease metabolic rate. Valproate failed to produce obesity in rats in any treatment period. For reasons that are unclear, rats do not appear to be suitable as a model to study this adverse side effect of VPA in humans with epilepsy.     

Effects of undernutrition on transit time and body weight of rats.

Rats given 50% and 25% of their ad lib food intake were taken as undernourished, while those on ad lib intake served as controls. Water was given ad lib for all rats. Body weight of all rats was measured daily. It showed decrease in undernourished groups but not to the extent expected from calorie intake. Fifty tiny (1-2 mm) orange coloured plastic markers mixed with food were given to all rats, at 11.00 p.m., and were collected from faeces at regular intervals of 1 h each till 80% of markers were obtained. Period (hrs) for collection of 80% markers was taken as total transit time. It showed increase with increased undernutrition (ad lib 38.9 +/- 2.1 hrs, 50% cal 68.2 +/- 5.3 hrs, 25% cal 105.00 +/- 3.3 hrs). Delayed transit time in the undernourished by prolonging contact period between food and absorptive surface of intestine probably caused increase in absorption of nutrients and thus counteracted against the loss in body weight of underfed rats.     

Methoxyflurane-induced nephrotoxicity: Influence of food intake on some biochemical indicators of renal function in Fischer 344 rats

The effect of methoxyflurane (MOF) anesthesia on food and water intake was measured in Fischer 344 rats which had been placed in an inhlation chamber containing 0.5% MOF for exposure times up to 6 hr. Pair-fed control rats were used to determine the role food intake plays in the renal toxicity observed after MOF administration. MOF anesthesia caused a dose-related decrease in the daily food consumption, body weight, and urinary osmolality, and an increase in the daily water intake and 24-hr urine volume. Administration of 0.5% MOF caused the daily food consumption to drop from 16.1 to 0.5 g/day/rat. Restricting the amount of food consumed per day by sham-treated Fischer 344 rats caused a decrease in body weight, daily water intake, and urine osmolality without changing the 24-hr urine volume (food deprivation for periods greater than 2 days resulted in a significant reduction in the 24-hr urine output). In MOF-treated rats, the increase in urine volume occurred prior to the increase in water intake. The loss in body weight and the decrease in excretion of solutes in the urine was the same for MOF-treated and pair-fed rats. The polyuria and polydipsia in MOF-treated rats was a result of the treatment unrelated to changes in daily food consumption.     

Interaction between estradiol replacement and chronic stress on feeding behavior and on serum leptin

Exposure to stress may cause either an increase or a decrease in food intake. Behavioral and physiological responses to stress, including alterations in feeding behavior, are sexually dimorphic. This study aimed to evaluate the interaction between estradiol levels and chronic variate stress on the intake of sweet food and on serum levels of leptin, a hormone secreted by the adipose cells with a role in the regulation of body weight. Adult female Wistar rats were used. After ovariectomy, the animals received estradiol replacement (or oil) subcutaneously. Rats were then divided in controls and stressed (submitted to 30 days of variate stress). Consumption of sweet food and of serum leptin was measured. Although animals receiving estradiol replacement presented smaller weight gain, they showed an increased consumption of sweet food. Chronic variate stress decreased sweet food intake at 30, but not at 20, days of treatment. Estradiol replacement in the stressed group prevented both the reduction observed in sweet food intake and the increase in leptin levels. These results suggest that there is an interaction between chronic stress and estradiol replacement in feeding behavior concerning sweet food consumption, and this interaction may be related to altered leptin levels.     

Imparied thermal regulation in juvenile rats following perinatal methadone exposure.

Offspring of female rats injected daily with methadone (5 mg/kg) or saline were cross-fostered at birth to form groups exposed to methadone during gestation (G), lactation (L), or gestation and lactation (G-L); controls (C) were exposed only to saline. Rectal temperature, body weight and food consumption were measured from postnatal Days 36-51. Ambient temperature was maintained at 21 degrees C except for Days 42--45, when the temperature was 10 degrees C. Group G rats never differed from controls, but offspring in Groups L and G-L were hypothermic at room temperature; Group G-L rats exhibited a further temperature loss during the cold stress. There were no group differences in food consumption after Day 39, and all groups increased food intake while in the cold. Group differences in body weight were not reliable but Group G-L rats gained less weight than the rest during the experiment, whereas Group L rats gained more. These results indicate that, depending upon treatment schedule, perinatal methadone exposure is associated with hypothermia during the postweaning period. A prolonged withdrawal reaction from methadone may account for the impaired thermal regulation.     

Nutritional status and spontaneous locomotor activity in the rat

A considerable amount of energy may be saved by lowering the spontaneous locomotor activity when energy intakes are reduced. The results of the present study in rats undernourished for a period of 21 or 60 days and subsequently fed ad libitum diet did not show any differences in activity when compared to their respective control groups, either during the undernourished periods or well fed states. Although this would mean that the rats are not economising energy on activity, it is probable that these rats with lower body weights are contributing to energy saving mechanism by reducing the cost of activity per se since the cost of activity and body weight are directly related.     

Amount and dietary sources of caffeine and saccharin intake by individuals ages 5 to 18 years

A nationwide, 7-day food consumption survey was utilized to assess average daily consumption of saccharin and caffeine by individuals 5 to 18 years old. The total sample's average daily saccharin and caffeine intakes were 4.1 and 37.4 mg, respectively. Only 14% of the individuals consumed saccharin while 98% consumed caffeine. On days when these dietary components were consumed, average saccharin intake was 87.4 mg and average caffeine intake was 47.9 mg. In general, intake levels of both dietary components increased with increasing age. However, on a body weight basis (mg/kg) caffeine intakes did not increase with increasing age. When expressed as milligrams of caffeine intake per kilogram body weight per day, children 5 to 6 years old had significantly higher intakes (1.1 mg/kg/day) than 7 to 8 year olds. No other age differences were noted. Artificially sweetened carbonated beverages contributed the greatest number of milligrams of saccharin to total intake while tea, followed by carbonated beverages, made the most significant impact on caffeine consumption. Considerable variation was found for both saccharin and caffeine consumption levels among the sample members as well as for each individual during the 7 days surveyed.     

Effects of repeated administration of serotonergic agonists on diet selection and body weight in rats

Food intake, diet selection and body weight gain were examined in three separate experiments in which rats received saline or one of three serotonergic agonists, dexfenfluramine, RU 24969 and fluoxetine. In all experiments, food was available only in the dark period during which time rats were given simultaneous access to two isoenergetic diets which differed in their protein and carbohydrate content. After habituation to this feeding paradigm and intraperitoneal injections, rats were assigned to control or drug group. Saline or a serotonergic agonist was given to the same rat once daily, 15 min prior to feeding, for six consecutive days. All three agonists (1.5 mg/kg for dexfenfluramine and RU 24969; 3 mg/kg for fluoxetine) caused immediate (first two h of feeding) hypophagia which was accounted for by the selective suppression in intake of the high-carbohydrate-low-protein diet. This selective shift in diet choice was sustained upon repeated exposure. Although the effects of these agonists on daily (12-h) feeding was less pronounced, appetite suppression was due entirely to reduced intake of the high-carbohydrate-low-protein diet. Of the three agonists tested, partial tolerance was observed only after dexfenfluramine. Nevertheless, all three agonists caused comparable declines in weight gain. These results suggest that repeated administration of serotonergic agonists has sustained impacts on food intake, diet choice and weight gain.     

Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions

Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage efter body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VMH lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggests a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.     

Unlimited access to heroin self-administration: independent motivational markers of opiate dependence.

The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state.     

Effect of chronic treatment with clomipramine on food intake, macronutrient selection and body weight gain in rats

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; 16th-18th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.     

Embryotoxicity and teratogenicity study with alpha-cyclodextrin in rats

The embryotoxicity/teratogenicity of alpha-cyclodextrin (alpha-CD) was examined in Wistar Crl:(WI)WU BR rats. alpha-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The additions to the diet of alpha-CD and lactose were made at the expense of pregelatinized potato starch. Body weight as well as food and water intake were recorded during the treatment period. The rats were killed on day 21 and examined for standard parameters of maternal reproductive performance. The fetuses were examined for external abnormalities, body weight and crown rump length. Fetuses were examined for skeletal and visceral abnormalities. Generally, alpha-CD was well tolerated and no deaths occurred in any group. Weight gain and food consumption were similar in all groups during gestation, except for a slightly yet significantly increased food intake in the 20% alpha-CD group from day 6 to 21. Water intake was similar in all alpha-CD groups; in the lactose group, it was significantly higher than in the controls. Maternal reproductive performance was not affected by the alpha-CD treatment. Examination of the fetuses for external, visceral and skeletal changes did not reveal any fetotoxic, embryotoxic, or teratogenic effects of alpha-CD. In conclusion, no adverse effects were observed at alpha-CD intakes of up to 20% of the diet, the highest dose level tested at which the rats consumed about 13 g/kg bw/day.     

Two-Generation Reproduction Study of Erythritol in Rats

Erythritol was fed at dietary concentrations of 0, 2.5, 5, or 10% to Crl:(WI) WU BR rats of both sexes through two successive generations (F₀and F₁). Twenty-four rats of each sex were mated in each group. For each generation one litter was reared until the pups were 21 days old. In the 10% erythritol group, food consumption among F₀-males and -females was initially significantly reduced until the animals adapted to the erythritol diet during the first week of the study. Thereafter, food intake was higher than in controls. A consistently increased food intake also was seen in F₁-males and -females of this dose group. This effect was considered to result from the caloric dilution of the food by erythritol, which has a low physiological energy value. The lower body weight and weight gain of the F₀-animals of the 10% erythritol group were attributed to the initially reduced food consumption and occurrence of transient diarrhea until the animals had adapted to the erythritol intake. In the F₁-animals of the 10% erythritol group, which were adapted to the treatment from weaning, the rate of body weight gain did not differ from controls. The F₁-males and -females of this dose group did, however, have a reduced body weight from weaning, which was attributed to a reduced energy intake among the corresponding F₀-dams during Weeks 2 and 3 of lactation. This effect was not seen in the F₂-generation. It is concluded that under the conditions of this experiment, the intake of erythritol had no adverse effect on fertility and reproductive performance of parent rats or on the development of their progeny. Gross necropsy and microscopic examination of the parenteral reproductive organs also did not reveal treatment-related changes.     

Nicotine's effects on female rats' body weight: caloric intake and physical activity

Caloric intake and physical activity contribute to the inverse relationship between nicotine and body weight in male rats. In contrast, the relative contribution of these behavioral variables to the nicotine/body weight relationship in female rats has has not been investigated. Recent research indicates that males and females respond differently to nicotine. The present study was designed to determine the role of physical activity and food consumption in body weight changes associated with nicotine administration in female rats. Nicotine or saline was administered chronically to 24 female rats for 19 days. Body weight, food consumption, water consumption, and physical activity were measured before, during, and after nicotine administration. Body weight and food consumption decreased during and increased after nicotine administration. However, there were no changes in physical activity that could account for these changes in body weight. These results corroborate the report that males and females respond differently to nicotine.