Chlordiazepoxide attenuates activity-induced anorexia and weight loss in rats.

Studied the effects of chlordiazepoxide (CDP) on body weight and food intake in male rats. In Exp 1, the effect of repeated injections of 2.5, 5.0, or 10.0 mg/kg of CDP on food intake and body weight was studied in rats on an activity anorexia (AA) regimen. For several days before CDP testing began, rats lived in activity wheels and had one 60-min meal/day. During CDP testing, this regimen continued except that each rat was injected with an appropriate dose of CDP or saline 30 min before each meal. CDP enhanced food intake; 5.0 mg/kg seemed most effective. However, the CDP-induced increase in eating did not noticeably stem weight loss. In Exp 2, after several days of AA training, CDP (5.0 mg/kg) was tested under less severe conditions; food remained restricted, but access to the wheels was discontinued. Rats given CDP ate more and gained more weight than controls. These findings suggest that benzodiazepines such as CDP may help in treating anorexia nervosa and other anorectic conditions in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolation and analysis of a gene bbe1 encoding the berberine bridge enzyme from the California poppy Eschscholzia californica

Rats experience anorexia and reduction or cessation in growth after being provided a zinc-deficient diet. While zinc deficient, intake levels may be reduced 50% or more compared to control rats. In the present report, diurnal food intake patterns of male Sprague-Dawley rats were measured during zinc deficiency. In Study 1, rats consuming a modified AIN-93 diet were tested during the dark phase using an automated food weighing system. In zinc-deficient animals (Zn-), the onset of the first meal of the dark phase was delayed compared to zinc-adequate rats (Zn+; 106+/-47 vs. 23+/-5 min; p<0.05) and the number of meals consumed during the dark phase was reduced in Zn- vs. Zn+ rats (3.9+/-0.5 vs 7.1+/-0.4; p<0.05). In Study 2, diurnal food intake patterns were tested using a three-choice macronutrient self-selection paradigm of carbohydrate-, protein-, and fat-containing diets made deficient or adequate in zinc (1 or 30 mg Zn/kg diet). Food intake was recorded in the early-, mid-, late-dark period (4 h each) and light period (12 h). Carbohydrate intake was 70% of total intake of both Zn+ and Zn- rats during the first 5 days, but decreased significantly to 50% in the Zn- group during the last 5 days. Fat intake increased significantly in the Zn- group during the last 5 days. This increase was the result of 4 of 15 Zn- rats increasing their intake of fat significantly. Results of this study indicate that zinc status alters dark phase and macronutrient selection patterns by delaying consumption of the initial meal of the dark phase, reducing the average meal number and by changing the dominant macronutrient preference of some Zn- rats.     

Food and water intake, meal patterns and activity of obese and lean Zucker rats following chronic and acute treatment with delta9-tetrahydrocannabinol

A series of experiments investigated the effects of delta9-THC on food and water intakes and wheel-running activity of Zucker rats. Following chronic drug treatment (15 days), food and water intakes of all rats were suppressed, but intakes and body weights of the obese rats recovered more slowly than those of lean rats. Acute effects of the drug (24 hr) were examined using techniques of meal pattern analysis and were discussed in relation to known patterns of anorectic drug action. The drug-induced anorexia was both delayed and of short duration, with no rebound eating observed for either solid or liquid diets. Both feeding rate and meal size were reduced, but meal frequency was transiently increased. The time of onset of the first meal remained unchanged. The time course of the suppression of feeding was paralleled by a suppression in running-wheel activity. These findings suggest that the drug-induced reduction in food and water intake may be the result of a decreased level of arousal.     

Adrenalectomy increases serotonin turnover in brains of obese Zucker rats

Because adrenalectomy tends to normalize many metabolic abnormalities of obese Zucker rats, we hypothesized that it would also normalize the depressed serotonergic turnover in their ventromedial nucleus (VMN). Lean (Fa/Fa) and obese (fa/fa) male Zucker rats were adrenalectomized or sham operated when 5 wks old and sacrificed at 11 wks. Their brains were frozen, and 13 areas were dissected for HPLC-EC analysis of monoamines and metabolites. Consistent with previous studies, VMN serotonin turnover (indexed by 5-HIAA/5-HT) was lower in obese than lean sham-operated rats. Monoamine and metabolite concentrations were altered in several other brain areas as well. Adrenalectomy reduced percent body fat and elevated VMN serotonergic turnover more in obese than in lean rats. It also stimulated serotonergic turnover in almost every brain area examined. We conclude that in obese Zucker rats: monoaminergic activity is altered in several brain areas involved in regulating energy balance; adrenalectomy normalizes the reduced VMN serotonergic turnover seen in the obese rats; and adrenalectomy results in a generalized increase in central serotonergic turnover. These data are consistent with serotonin's role in inhibiting food intake and enhancing sympathetic stimulation of energy metabolism.     

The effect of the volatile oils of Chenopodium ambrosioides and Thymus vulgaris against the larvae of Lucilia sericata (Meigen)

We have isolated a stable, transplantable, and small glucagonoma (MSL-G-AN) associated with abrupt onset of severe anorexia occurring 2-3 wk after subcutaneous transplantation. Before onset of anorexia, food consumption is comparable to untreated controls. Anorexia is followed by adipsia and weight loss, and progresses rapidly in severity, eventually resulting in reduction of food and water intake of 100 and 80%, respectively. During the anorectic phase, the rats eventually become hypoglycemic and hypothermic. The tumor-associated anorexia shows no sex difference, and is not affected by bilateral abdominal vagotomy, indicating a direct central effect. The adipose satiety factor leptin, known to suppress food intake by reducing hypothalamic neuropeptide Y (NPY) levels, was not found to be expressed by the tumor, and circulating leptin levels were reduced twofold in the anorectic phase. A highly significant increase in hypothalamic (arcuate nucleus) NPY mRNA levels was found in anorectic rats compared with control animals. Since elevated hypothalamic NPY is among the most potent stimulators of feeding and a characteristic of most animal models of hyperphagia, we conclude that the MSL-G-AN glucagonoma releases circulating factor(s) that overrides the hypothalamic NPY-ergic system, thereby eliminating the orexigenic effect of NPY. We hypothesize a possible central role of proglucagon-derived peptides in the observed anorexia.     

RNA virus in Allomyces arbuscula: ultrastructural localization during the life-cycle

Three experiments were concerned with tolerance to anorexia induced by d-amphetamine. In experiment 1, one group of rats on a 2 hr food deprivation schedule received 2 mg/kg of d-amphetamine 15 min before eating every other day for a month. A second group of rats on a similar schedule received the same dose of d-amphetamine immediately after eating. When compared to a saline-treated control group, the former group showed significant decreases in weight and food intake; tolerance to the amphetamine-induced anorexia began to occur toward the end of the experiment. The latter group showed a significant decrease in food intake on the non-drug days and an overall weight loss when compared to the control group. Experiment 2 demonstrated that tolerance to d-amphetamine-anorexia was related to the duration of drug administration per se. Experiment 3 showed that taste can be a factor in influencing the rate of tolerance to d-amphetamine-induced anorexia. These results indicate that both pharmacological and experiential factors play an important role in determining the rate of tolerance to this action of d-amphetamine.     

Central effects of dehydroepiandrosterone in Zucker rats

OBJECTIVES: To investigate whether dehydroepiandrosterone (DHEA), an adrenal/gonadal androgen, can act centrally to reduce energy intake in a model of genetic obesity, the Zucker fatty rat. To investigate a possible mechanism of action. DESIGN: Two experiments were performed in lean and obese female Zucker rats. In the first experiment, 24 h following administration of i.p. DHEA (200 mg/kg), three hypothalamic regions [lateral hypothalamus (LH), ventromedial nucleus (VMH), and paraventricular nucleus (PVN)] were analyzed for monoamine neurotransmitter concentrations. In the second experiment, DHEA (50 micrograms) was administered by i.c.v. injection. Energy intake for the following day was measured. MEASUREMENTS: In the first experiment, concentrations of norepinephrine (NE), epinephrine (EPI), dopamine (DA), serotonin (5HT), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured. Ratios of 5HT/5HIAA were calculated. In the second experiment, kilojoules consumed per 24 h were calculated. RESULTS: All LH monoamines, and PVN DA, displayed lower concentrations in obese than lean control rats. DHEA treatment reversed these reductions in obese rats without affecting lean rats. DHEA increased VMH EPI in obese rats only. DHEA increased PVN NE in both lean and obese rats. I.C.V. DHEA decreased energy intake in obese but not lean rats. CONCLUSION: The i.c.v. results suggest that DHEA exerts a phenotype specific, centrally mediated inhibitory effect on food intake. In addition, in doses previously shown to reduce energy intake in obese but not lean rats, i.p. DHEA reversed reduced concentrations of many monoamines, particularly in the LH, in obese animals only. These latter changes provide indirect evidence to suggest that these central neurotransmitters may play an important role in the antiobesity effect of DHEA in the Zucker fatty rat.     

Chlordiazepoxide counteracts activity-induced suppression of eating in rats.

Because benzodiazepines such as chlordiazepoxide increase food intake, the present experiments tested the effect of chlordiazepoxide on food intake in an animal model of anorexia nervosa, called activity anorexia (AA). To induce AA, rats (Rattus norvegicus) were maintained in activity wheels and restricted to a single 60-min feeding period each day. As previously found, this procedure suppressed food intake. After several days of this training, food intake was measured 30 min after the rats were injected with chlordiazepoxide (5 mg/kg) or saline. In 2 experiments, chlordiazepoxide counteracted the suppression of food intake produced by AA. Because benzodiazepines have been found to increase food intake in many mammalian species including primates, the present results suggest that benzodiazepines could be useful in the treatment of anorexia nervosa. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carnitine supplementation accelerates normalization of food intake depressed during TPN

When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.     

Some effects of conditioned aversion on food intake and olfactory bulb electrical responses in the rat

Rats maintained on an unadulterated synthetic food, available from 8 a.m. to 10 a.m. everyday, were submitted to an aversive conditioning schedule on which a first ingestion of eucalyptol-flavored food (EF) was followed by an apomorphine injection (20 mg/kg, ip). In the first experiment the daily food intake was measured from Day 1 to 17, during the first and second hours of the meal. The EF was offered on Days 8, 9, and 17 during the first or the second hour of the meal (Series B or A). On Day 8, the meal was followed in a group of rats by the apomorphine injection. As compared with the intake of Day 8, the mean EF intake of Day 9 was significantly decreased in Series A and B, and of Day 17 in Series A only. No significant EF-intake modification could be observed in a saline-injected group or in an untreated control group. In the second experiment, rats bearing bulbar electrodes for the chronic recording of multiunit mitral cell responses received a 2-hr EF meal before the apomorphine injection. They were stimulated by puffs of odors of pure eucalyptol, unadulterated food, and EF and recorded in hungry and satiated states. Before the aversive conditioning, a significantly greater occurrence of positive responses to the odors of unadulterated food and EF was observed in hungry rats compared with satiated rats. The eucalyptol odor yielded equivalent patterns of responses in hungry and satiated rats before and after conditioning. Conditioning did not alter the modulated responses to unadulterated food odor (a greater occurrence of positive responses was still observed in hungry rats) but modified the responses to the odor of EF (the same high rate of positive responses was then observed in satiated and hungry rats). Electrophysiological data are discussed in terms of palatability changes and food-odor meaning.     

CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions

Male rats were injected with 6-hydroxydopamine in the lateral hypothalamus and tested for ingestive behavior starting on the day after the injection. The rats did not eat food pellets but readily ingested an intraorally infused nutritive solution. If given three daily intraoral infusions, 6-hydroxydopamine-treated rats defended their body weight and were as sensitive to the inhibitory effect of cholecystokinin octapeptide on intake as controls. Dopamine was reduced by 94% in the dorsal striatum five days after the 6-hydroxydopamine injection. Noradrenaline and serotonin were less markedly affected. Thus, while appetitive ingestive behavior is disrupted, consummatory ingestive behavior and body weight regulatory competence are only marginally affected by massive damage to forebrain dopamine neural networks.     

Effects of food restriction on the periodicity of corticosteroids in plasma and on monoamine concentrations in discrete brain nuclei

The concentrations of plasma corticosteroids and of norepinephrine, dopamine and serotonin in microdissected brain regions were measured at 08.00, 12.00 and 20.00 h in male rats fed ad libitum and in rats whose food intake was restricted to 09.30-11.30 h. In ad libitum fed animals, plasma corticosteroids were lowest at 08.00 and highest at 20.00 h. As demonstrated previously, restriction of food availability was associated with appearance of a peak in corticosteroids at 08.00 h. In ad libitum fed animals, serotonin and dopamine concentrations in the median eminence were higher at 20.00 than at 08.00 h. Restriction of food availability significantly decreased the levels of these neurotransmitters at 20.00 h. In the paraventricular nucleus, amygdala, and hippocampus of ad libitum fed animals, serotonin levels were lower at 20.00 than at 08.00 or 12.00 h. In food-shifted animals, this pattern was reversed so that lowest levels of serotonin occured at 08.00 and markedly elevated levels were observed at 12.00 and 20.00 h. No changes were noted in norepinephrine content of the median eminence or paraventricular nucleus of ad libitum fed or food restricted animals. These results indicate that the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regime is accompanied by changes in the periodicity of neurotransmitter concentrations in specific regions of the brain, and that such patterns are dissimilar in different regions.     

The ethical problem of the health-environment relationship]

The effects of sustained stress on response rate and temporal patterning (quarter-life) of rats performing either a previously learned fixed-interval schedule (FI 60) or learning an FI 60 simultaneously with stress onset were determined. Rats lived 24 h/day in operant cages, where they earned all of their food via lever-pressing. During the stress portion of each experiment, one group of rats was able to avoid or escape signalled intermittent footshock (Avoidance/ Escape Group), a second group (Yoked) did not have control over shock termination, a third group never received shock (Control). Shock trials were presented around the clock at approximately 5-min intervals and the stress portion of each study lasted 1-2 weeks. We have previously reported that rats tolerate this paradigm well and avoid/escape 99% of the shock trials. In rats previously trained on the FI task, both rate of responding and quarter-life values were significantly decreased on the first day of stress for both the Avoidance/Escape and Yoked Groups. Food intakes and quarter-life values were not significantly different from the controls by stress Days 3 and 2, respectively. In the acquisition study, controls learned the F1 task by Day 4 as judged by quarter-life of responding. FI task acquisition was significantly impaired in stressed rats compared to controls, not reaching asymptotic performance until Day 9 of stress. There were no major differences between the 2 stress groups in either study. These data demonstrate that stress may impair both the rate and patterning of behavior, and suggest that this rodent paradigm may usefully model some aspects of the effects of stress in humans.     

Mesencephalic lesions resulting in normophagia, reduced weight and altered metabolism

The effects of bilateral lesions of the ventral noradrenergic bundle (VNA) were studied in male rats. In contrast to data reported by others, hyperphagia and obesity were not observed following VNA lesions. Indeed, except for a depression during the first three postoperative days, food intake (FI) of the VNA lesioned animals (VNAL) was normal. Interestingly, the body weight (BW) of the VNAL was significantly reduced compared to the controls, and a pair feeding study indicated that this depression of BW was not due to their FI. Computation of FI per metabolic size showed that the VNAL actually had a significantly increased FI compared to the controls. After a two day fast the VNAL lost more metabolic size than controls and upon refeeding they defended their pre-fast BW. The VNAL rats showed normal body composition and circulating glucose, insulin and prolactin. They had reduced free fatty acids, triglycerides, growth hormone and body length. The data suggest that the mesencephalon influences BW set point, some metabolites and possibly overall metabolism.     

Effects of ovariectomy on meal pattern in the albino rat.

In a study with 24 female albino Sherman rats, it was found that after ovariectomy most Ss increased food intake while continuing to eat discrete meals. Meal size increased in ovariectomized Ss, whereas meal frequency decreased. It is suggested that ovariectomy impairs the onset of satiety during a meal but not the ability to regulate total intake through modification of intermeal interval. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bacterial toxins block endothelial wound repair. Evidence that Rho GTPases control cytoskeletal rearrangements in migrating endothelial cells

Pharmacological experiments were conducted to determine the neuronal mechanisms involved in the suppressive effects of the thyrotropin-releasing hormone analog TA-0910 on alcohol intake in alcohol-preferring (P) rats. We previously reported that single intraperitoneal injections of TA-0910 dose-dependently reduced alcohol intake in P rats without altering fluid or total calorie intake; however, after several consecutive, once-daily injections, P rats developed tolerance to the suppressive effects of TA-0910 on alcohol intake and cross-tolerance to like effects of the dopamine D2 agonist bromocriptine, but not to like effects of the serotonin uptake inhibitor fluoxetine. In the present study, rats were injected with vehicle or different doses of the D2 antagonist s(-)-eticlopride (0.01 to 0.05 mg/kg) or the D1 antagonist R(+)-SCH23390 (0.1 to 0.5 mg/kg) and 20 min later with TA-0910 (0.75 mg/kg). Alcohol and water intakes were measured at 2, 4, 6, and 24 hr, and food was measured every 24 hr. Both s(-)-eticlopride and R(+)-SCH23390 produced modest reductions in alcohol intake alone; however, only s(-)-eticlopride antagonized the suppressive effect of TA-0910 on alcohol intake. In related experiments, it was confirmed that the dopamine D3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin reduced alcohol intake in P rats, and it was found that tolerance to this effect did not develop during or after seven consecutive once-daily injections. Furthermore, this effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetralin was not diminished in rats made tolerant to the effect of TA-0910 on alcohol intake. These data, those of previous studies, and recent preliminary findings support involvement of dopamine D2, but not D1 or D3 receptors in mediating the suppressive effect of TA-0910 on alcohol intake of P rats.     

Functional osseointegration of hydroxyapatite-coated implants in a weight-bearing canine model

The serotonin3 receptor antagonist ICS 205-930 (ICS) may act peripherally to attenuate the anorectic response of rats given an imbalanced amino acid (IMB) diet. Rats were divided into four groups: SHAM+saline (sal); SHAM+ICS; total liver denervation (TLD) + sal; and TLD+ICS. Rats were then given a purified basal diet for 16 days. Next, the groups were injected with sal or 9 mg/kg BW of ICS at 0800 h and at 0900 h (lights out) an isoleucine IMB diet was presented. By 12 h postinjection, the food intake (FI) of TLD and SHAM rats receiving ICS was similarly higher (p < 0.02) than sal-injected counterparts whose FI was also similar; BW followed FI. By day 3, the SHAM groups had similar low FI, whereas the FI of the TLD groups was increasing. The above study was repeated with similar results. Liver innervation is not required for ICS attenuation of IMB diet-induced hypophagia. Also, while sal-injected TLD rats show a normal attenuation of consumption of the IMB diet on the first day of exposure, they subsequently consume more of the IMB diet than SHAM rats. The reason for this difference in TLD rats is not clear but may be related to metabolism of the IMB diet or possibly learning.     

Acute intraventricular CRF lowers the hoarding threshold in male rats

The influence of intracerebroventricular rat-CRF on the food-hoarding behavior of rats has been studied in relation to the animals' body weights. A group of six male rats was trained to feed every day from 1000 to 1200 h. Then their threshold for the onset of food hoarding was measured from the intercept of regression line of food hoarded during meal time vs. body weight with the x-axis. Thirty minutes before the hoarding session, the rats received 4 micrograms CRF, or saline control, in the lateral ventricle. The mean threshold for food hoarding was significantly lowered to 299 +/- 61 g after CRF, from control 418 +/- 68 g. Mean food intake during the hoarding sessions was also diminished to 6.0 +/- 0.6 g after CRF, from control 14.5 +/- 0.5 g. These results suggest that the set-point for body weight regulation is acutely lowered by intracerebral CRF.