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.     

Effects of chronic haloperidol treatment on ingestive behaviour and body weight regulation in the rat

This study was designed to investigate the effects of two doses of haloperidol on body weight, food spillage and food and water intake using rats as subjects. In the first experiment, 12 male Wistar albino rats were observed in individual cages for 30 days, six receiving a daily injection of haloperidol (1 mg/kg IP in 1 ml/kg isotonic saline), while the other six received a control injection of isotonic saline in the experimental phase. In the second experiment, 12 rats were observed for 9 days in individual cages, six receiving a daily injection of 10 mg/kg haloperidol in 4 ml/kg isotonic saline in the experimental phase. In both studies, haloperidol depressed food intake and food spillage. With the lower dose of haloperidol (1 mg/kg), body weight was not depressed until several days after a significant reduction of food intake had been recorded. With the higher dose (10 mg/kg), body weight was depressed during the first 24 h, but quickly returned to normal, although food intake remained depressed. It is suggested that haloperidol may have a limited facilitatory effect on body weight.     

Teratological studies in defatted jojoba meal-supplemented rats.

To look for possible developmental effects in the offspring of jojoba meal-treated Wistar rats, and to distinguish between the effects of reduced food intake and the specific developmental effects of jojoba meal itself, mated female rats were divided into three groups of 20 rats. They received during gestation: (a) normal rodent food (control group); (b) normal rodent food supplemented with 3% defatted jojoba meal (jojoba group); or (c) normal rodent food pair-fed with the jojoba group (pair-fed group). The jojoba meal group showed approximately 30% inhibition of food intake. Ten rats from each group were killed on gestation day 21. Compared to the control group, foetal body weight was reduced in both the jojoba and pair-fed groups, with a greater reduction in the jojoba group. Skeletal ossification was retarded to the same extent in both the jojoba and pair-fed groups. The other 10 rats from each group were left to produce litters. Compared with controls, the body weight of the pups was lower in both the jojoba and pair-fed groups; the reduction was slightly greater in the jojoba group, but this difference disappeared after 1 week. The offspring showed no other abnormalities and reproduced normally. We conclude that, at the dose used, the retardation in foetal skeletal ossification, induced by jojoba meal supplementation during gestation, is due to food intake inhibition. Moreover, the lower birth weight of the young of jojoba-treated dams compared with the pair-fed group is merely due to a lower body weight gain during gestation.     

Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats

Rationale and objectives Previous work indicated that tolerance to the anorectic effect of the cannabinoid CB₁ receptor antagonist/inverse agonist, rimonabant, developed rather rapidly in rats and mice given access to a standard rodent chow. The present study was designed to investigate whether the reducing effect of rimonabant on intake of a highly palatable food such as a chocolate-flavoured beverage underwent a development of tolerance as rapid as that manifested on intake of a standard rodent chow. Materials and methods To this aim, Wistar rats were concurrently exposed, with unlimited access for 24 h/day, to the chocolate-flavoured beverage, regular food pellets and water. Rimonabant (0, 1.25, 2.5 and 5 mg/kg; i.p.) was administered once a day for 21 consecutive days. Results Rimonabant administration resulted in a dose-dependent suppression of the high, daily intake of the chocolate-flavoured beverage; this effect lasted for the entire 21-day treatment period, without any apparent development of tolerance. Conversely, rimonabant-induced reduction in daily intake of regular food pellets was of a smaller magnitude and was limited to the first 3–4 days of treatment. Conclusions Together, these results indicate that chronically administered rimonabant was more effective and longer-lasting in reducing the intake of a highly palatable food than that of regular food pellets in rats. These results also suggest that rimonabant may be more active on the hedonic rather than nutritive properties of diets.     

Effect of immobilization stress on food intake, body weight and weights of various organs in rat

Effect of immobilization stress was studied in male albino rats. Experimental rats (E) were restrained in close-fitting wiremesh cylinders. Control rats (C) were not subjected to restraint. Food and water were made available to C for all the 24 hrs while the E were given them for only 6 hrs daily. The initial lower food intake of E was later reversed to near normal levels. There was a steady fall in the body weights of E, while the C displayed a normal growth rate. Cerebrum, cerebellum, pituitary and adrenals of E weighted significantly more. There was an apparent increase in the weight of thyroid. Gonads displayed no change in weight. The results indicate that chronic restraint causes loss of body weight inspite of a near normal food intake. It also produces an increase in the weight of brain, and certain endocrine organs.     

Differential effects of chronic naltrexone treatment on food intake patterns and body weight in rats depend on their food deprivation status

The aim of the present study was to assess the effect of chronic naltrexone treatment on daily patterns of food intake in food-deprived and free-feeding rats. In experiment 1, Wistar male rats had continuous access to food and water, while in experiment 2 they were deprived of food for 12 h/day. Animals in both experiments were studied as follows: a baseline period (7 days), followed by a treatment period (14 days) with either saline or naltrexone at 10 mg/kg/day. Finally, a post-treatment period (7 days) was assessed. Food and water consumption were measured every 2 h after the naltrexone or saline injection for 12 h and once more 12 h later. Experiment 1: Food intake was higher in the naltrexone group 10 h after injection. Total food intake and body weight gain were higher in the naltrexone group than in the saline group in the second week of treatment and in the post-treatment period. Experiment 2: The overeating observed in the saline group in the hours following the 12 h of the food deprivation period was suppressed by naltrexone, though total daily food intake was not affected. Body weight gain was initially reduced by naltrexone, but a rebound effect was observed during the post-treatment period in the naltrexone group. Naltrexone produced a differential effect on food intake and body weight that depended on the rats' food deprivation status. These results could be explained in terms of opioid receptor up-regulation that enhances the rewarding effects of food or by naltrexone-produced changes in palatability.     

Effects of chronically administered fluoxetine and fenfluramine on food intake,body weight and the behavioural satiety sequence

Rats were administered fenfluramine (FF: 3 mg/kg) or fluoxetine (FX: 6 mg/kg) daily for 3 weeks. On acute administration, FF suppressed consumption of 35% sucrose (in a 40 min test) and overnight chow intake. Repeated administration saw the rapid development of extensive tolerance to these effects. FF had no effects on body weight, and no withdrawal effects were apparent. FX reduced chow intake and body weight throughout the treatment period, but there was evidence of some tolerance to the suppression of chow intake and sucrose drinking. Following FX withdrawal, normal body weight was restored in 4 days; food intake was normal during this period. A delayed rebound hyperphagia commenced on day 5 of withdrawal, and persisted for at least 6 days. The behavioural satiety sequence (drinking -activity - grooming - resting) was disrupted by acute FF; on chronic treatment, FF advanced the onset of postprandial resting, but also increased drinking time. FX advanced the behavioural satiety sequence on acute administration, but not after chronic treatment. We consider the implications of these results for the use of resting behaviour as an indicator of postprandial satiety.     

Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food.

Binge eating and an increased role for palatability in determining food intake are abnormal adaptations in feeding behavior linked to eating disorders and body weight dysregulation. The present study tested the hypothesis that rats with limited access to highly preferred food would develop analogous opioid-dependent learned adaptations in feeding behavior, with associated changes in metabolism and anxiety-like behavior. For this purpose, adolescent female Wistar rats were daily food deprived (2 h) and then offered 10-min access to a feeder containing chow followed sequentially by 10-min access to a different feeder containing either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable, sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge-like hyperphagia of preferred diet from the second feeder and anticipatory chow hypophagia from the first feeder with a time course suggesting associative learning. The feeding adaptations were dissociable in onset, across individuals, and in their dose-response to the opioid-receptor antagonist nalmefene, suggesting that they represent distinct palatability-motivated processes. Chow/preferred-fed rats showed increased anxiety-like behavior in relation to their propensity to binge as well as increased feed efficiency, body weight, and visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short-term control of food intake in rats with restricted access to highly preferred foods comes to rely more on hedonic, rather than nutritional, properties of food, through associative learning mechanisms. Such rats show changes in ingestive, metabolic, endocrine, and anxiety-related measures, which resemble features of binge eating disorders or obesity.     

3-O-beta-D-glucosyl-(1-->6)-beta-D-glucosyl-kaempferol isolated from Sauropus androgenus reduces body weight gain in Wistar rats

The young sticks and leaves of Sauropus androgynus (SA) that had been used as a health food for body weight reduction, led to an outbreak of obliterative bronchiolitis in Taiwan. This study tested the toxicity and anti-obesity features of the SA-isolated compound, 3-O-beta-D-glucosyl-(1-->6)-beta-D-glucosyl-kaempferol (GGK), on male Wistar rats receiving 6 or 60 mg/kg of GGK orally as well as partial purified EtOAc and n-BuOH fractions of SA extract daily for 28 d. Sixty milligrams per kilogram GGK treatment significantly reduced food intake in rats by 15% (p<0.05). The reduced food intake corresponded to decreases in body weight in the high or low dose GGK groups, as compared to the control groups. The serum levels of free triglyceride significantly decreased in GGK-treated rats. GGK treatment led to succesive reductions in daily food intake and body weight without obvious histopathological changes in Wistar rats. Thus, GGK may be potentially to be developed as a safe and novel compound for anti-obesity treatment.     

Meal patterns and body weight after nicotine in male rats as a function of chow or high-fat diet

Studies of the effects of nicotine (NIC) on meal patterns in rats often employ chow pellet diets that contain little fat, whereas humans using NIC commonly consume diets relatively rich in fat. The aim of the present study was therefore to compare the impact of NIC administration and NIC cessation on meal pattern in adult male rats offered a standard powdered chow (CHOW: 10.9% fat by calories) diet or a palatable high-fat (HIFAT: 58.3% fat by calories) diet. Computerized meal pattern analyses were conducted for male rats treated for 14 days with injections of either saline or 1.4 mg/kg/day of NIC (as the free base given in 5 equal amounts) during the dark phase and continued for 10 days after NIC cessation. The suppression of daily caloric intake by NIC was larger in HIFAT-NIC rats than in CHOW-NIC rats (p < .01), such that NIC induced a greater suppression of body weight in HIFAT-NIC rats, relative to CHOW-NIC rats (p < 0.02). NIC administration reduced MS in both CHOW and HIFAT rats. CHOW fed rats showed a gradual increase in meal number in response to NIC, whereas HIFAT fed rats showed a significant initial suppression of meal number, which returned to control levels by day 4 of the 14 day NIC treatment period. In addition, NIC increased water intake more in HIFAT fed rats than in CHOW rats. Cessation of NIC resulted in transient increases in daily caloric intake in CHOW and in HIFAT rats. The present study demonstrates that NIC actions on food intake suppression, meal patterns, and weight reduction differ depending on whether the rats are fed low- or high-fat diets.     

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.     

Effects of chronic phenylpropanolamine infusion and termination on body weight,food consumption and water consumption in rats

The present study determined the effect of chronic PPA infusion and withdrawal on weight regulation. Male Sprague-Dawley rats received PPA (0, 90 or 180 mg/kg) via miniosmotic pumps for 2 weeks. Body weight and food and water consumption were measured daily before, during, and for 2 weeks after PPA infusion. Additionally, body weight was measured once 6 weeks after the last day of drug administration. PPA infusion produced dose-dependent reductions in body weight and food consumption throughout drug administration. During the first week of PPA termination, food consumption returned to control levels; however, body weights of drug-treated animals remained below those of controls throughout the 6-week post-drug period. PPA depressed water intake during the first week of drug administration, but tolerance to this effect developed by the second week of administration. These results suggest chronic PPA infusion produces persistent appetite suppression and weight loss and that discontinuation of PPA does not result in hyperphagia or rapid weight gain. These findings may have clinical significance for the many individuals who wish to lose weight but have difficulty reducing intake without pharmacologic assistance.     

Clinical and biochemical effects of citalopram,a selective 5-HT reuptake inhibitor — a dose-response study in depressed patients

The effect of repeated administration of desipramine (DMI) on the acquisition, performance, and extinction of a lever press response for food reward was studied. Chronic administration of DMI caused a reduction in pressing under a CRF schedule both in naive and well-trained rats. Responding during extinction sessions did not differ between saline-treated rats and rats given DMI chronically. In addition, chronic administration of DMI reduced the body weight and food intake of rats on either a free-feeding or a restricted-feeding schedule. Consequently, lever pressing was also studied in a group of rats whose body weight was regulated to match the body weight of rats were administered DMI chronically. In comparison to this control group, rats administered DMI chronically responded significantly less during both reinforcement and extinction sessions. These results fail to replicate earlier reports that chronic DMI administration produces increased resistance to extinction. The results also show that assessment of food-motivated performance in rats treated chronically with DMI is difficult because of long-term changes in body weight and food intake.     

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.     

Long-term effects of TRH administration on food intake and body weight in the rat

The effect of long-term TRH administration through drinking water (0.2 mg/ml) on food and water intake and body weight has been studied in three groups of female rats: (1) thyroidectomized, (2) thyroidectomized receiving daily 250 micrograms/kg of L-T4, (3) sham-operated. Treatment with oral TRH for 30 days decreased body weight and increased food intake in sham-operated rats. No TRH effects on body weight or food consumption were observed in either of the other groups of thyroidectomized rats. TRH administration increased circulating T3 levels in sham-operated animals, but had no effects in either hypo- or hyperthyroid, thyroidectomized rats. It can be concluded that the TRH-induced increase on food intake is mediated through the pituitary-thyroid axis.     

Safety assessment of yerba mate (Ilex paraguariensis) dried extract: results of acute and 90 days subchronic toxicity studies in rats and rabbits

Acute toxicity of yerba mate dried extract (YMDE) was investigated in Wistar rats (6/sex/group) from single dose of 2g/kg body weight by intragastric administration and 14days monitoring. Subchronic toxicity was investigated in Wistar rats, by intragastric administration (10/sex/group), and in New Zealand rabbits by oral administration (3/sex/group) of 2g/kg body weight for 12weeks. Toxicological parameters included clinical signs, body weight, water, and food consumption, hematological and serum parameters, and histopathological assessment. Acute YMDE administration showed no effects on survival, clinical observations, macroscopic examination of organs, body weight or food, and water consumption. Sub-chronic administration of YMDE did not change behavior, body weight, and histopatological assessment of stomach, kidney, liver, and small gut. Moreover, most of biochemical and hematological parameters remained unchanged. In summary, the results of our preclinical toxicological investigation are indicative that the YMDE is well tolerated for both single and chronic administration.     

Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

Several clinical reports have demonstrated that most antipsychotics of the new generation, but not the typical antipsychotic haloperidol, induce weight gain in schizophrenic patients. Since weight gain induces serious health complications in humans, it is crucial to test upcoming antipsychotic compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic not inducing weight gain in clinic (haloperidol), on food and water intake and body weight gain in rats. We included both female and male rats in this study. To reduce spontaneous high food intake in rats, and to be able to evaluate the treatment effect on a potential increase of food intake or metabolic changes, we allowed animal to receive only low-palatability chow. In male rats, none of the two compounds induced weight gain, but in female rats, both compounds induced weight gain. Consequently, the effect observed in rats does not match the clinical situation, and Wistar rats in this set-up cannot be considered a relevant model for antipsychotic-induced weight gain in humans.     

Influence of tetrahydrocannabinols (delta8-THC and delta9-THC) on body weight, food, and water intake in rats

Female Wistar rats, six to a group, were injected daily for a 23-day period with Δ⁸-THC (5.0 mg/kg), Δ⁹-THC (2.5 mg/kg) or vehicle. Body weight, food and water intake were recorded every second day. It was found that Δ⁸-THC caused a decrease of body weight, to a level maintained throughout the injection period, with only slight signs of recovery. Both drugs caused a marked decrease of water intake. Food intake was not significantly affected by the drugs. Factors in relation to the effects of THC on body weight, food and water intake are discussed.     

Effects of a chronic administration of two benzodiazepines on food intake in rats given a highly palatable diet

Chronic administration of benzodiazepines is known to increase food intake in numerous species. But this effect has been studied only after a unique daily injection and over a short part of the 24 hr cycle. In the present study, during 28 days, drugs were administered to rats receiving ordinary chow or a highly palatable diet (cafeteria diet): diazepam (DZ) (2.5 mg/kg IP) twice a day, or brotizolam (BR) (1 mg/kg IP), a longer acting compound, once a day. In the chow fed rats, DZ and BR provoked a post injection hyperphagia throughout the study, followed by a compensatory hypophagia resulting in 24 hr food intakes not different from those of controls; conversely neither body weight nor weight of fat pads were increased. The cafeteria diet provoked hyperphagia and overweight. DZ did not induce any supplementary hyperphagia. BR provoked a post injection hyperphagia, also compensated in time, resulting again in 24 hr food intakes, body weight gains and weight of fat pads not increased compared to those of cafeteria controls. Thus in the rat, benzodiazepine treatment increases food intake, but only acutely, and does not provoke any trend toward obesity.     

Food deprivation reveals strain differences in opiate intake of Sprague-Dawley and Wistar rats

Two groups of naive, male, albino rats derived from different genetic strains (Sprague-Dawley and Wistar) were given a 5 micrograms/ml etonitazene solution as their only available liquid. Liquid intake and body weights were recorded every 24 hr. Etonitazene intake was compared to baseline water intake, and drug intake was then compared when the rats were food deprived (25 sessions) and food satiated (24 sessions). Both groups drank similar amounts of water and etonitazene during the initial food satiation phase, although drug intake was slightly below water intake. When they were food deprived, the Wistar group's mean etonitazene intake almost doubled, while the Sprague-Dawley group's drug intake decreased by nearly 50%. The etonitazene intake in the Sprague-Dawley group never exceeded that of the vehicle, water; thus, it appeared that the drug was not functioning as a reinforcer. Food deprivation increased etonitazene intake above water levels in the Wistar group, indicating that the drug was serving as a reinforcer. Both groups showed similar drug effects during food deprivation, such as erratic drinking patterns, self-mutilation and other forms of stereotypy. Thus, both strains were sensitive to etonitazene's effects; they appeared to differ only with respect to the reinforcing effects. These results suggest that genetically-based differences in the reinforcing effects of drugs may be revealed by food deprivation.