GABAergic control of food intake in the meat-type chickens

This study examined the effects of intracerebroventricular injections of gamma-aminobutyric acid (GABA) agonists on short-term food intake in meat-type cockerels. In Experiment 1, birds were injected with various doses of muscimol, a GABA(A) agonist. In Experiment 2, the birds received bicuculline, a GABA(A) antagonist, prior to injection of muscimol. In Experiment 3, the effect of varying doses of baclofen, a GABA(B) agonist, on food intake was determined. The intracerebroventricular injection of muscimol caused a dose-dependent increase in food intake. This effect was significantly attenuated by pretreatment with bicuculline. Food intake was not affected by the intracerebroventricular injection of baclofen. These results suggest that GABA acts within the brain of broilers at a GABA(A), but not GABA(B), receptor to increase voluntary food intake.     

Inhibition of food intake by CRF in chickens.

The effect of intracerebroventricular (i.c.v.) injection of corticotrophin releasing factor (CRF) on food and water intake and on body temperature in chickens was determined. Both broiler and Leghorn type chickens were utilized in this experiment. A stainless steel guide cannula was surgically implanted into the right lateral ventricle of each bird. The i.c.v. injection of CRF significantly decreased food intake in both fed and overnight-fasted broilers and Leghorns. Water intake was decreased by CRF in Leghorns but not broilers. When CRF was injected into Leghorns given access to water, but not food, water intake was not affected. Body temperature was not affected by the i.c.v. injection of CRF. These results suggest that CRF acts within the central nervous system of chickens to decrease food intake while having no affect on water intake or body temperature.     

The role of GABAergic system on the inhibitory effect of ghrelin on food intake in neonatal chicks

Ghrelin is a gut-brain peptide that has a stimulatory effect on food intake in mammals. In contrast, this peptide decreases food intake in neonatal chicks when injected intracerebroventricularly (ICV). In mammals, neuropeptide Y (NPY) mediates the orexigenic effect of ghrelin whereas in chicks it appears that corticotrophin releasing factor (CRF) is partially involved in the inhibitory effect of ghrelin on food intake. Gamma aminobutyric acid (GABA) has a stimulatory effect on food intake in mammals and birds. In this study we investigated whether the anorectic effect of ghrelin is mediated by the GABAergic system. In Experiment 1, 3 h-fasted chicks were given an ICV injection of chicken ghrelin and picrotoxin, a GABA_A receptors antagonist. Picrotoxin decreased food intake compared to the control chicks indicating a stimulatory effect of GABA_A receptors on food intake. However, picrotoxin did not alter the inhibitory effect of ghrelin on food intake. In Experiment 2, THIP hydrochloride, a GABA_A receptor agonist, was used in place of picrotoxin. THIP hydrochloride appeared to partially attenuate the decrease in food intake induced by ghrelin at 30 min postinjection. In Experiment 3, the effect of ICV injection of chicken ghrelin on gene expression of glutamate decarboxylase (GAD)₁ and GAD₂, GABA synthesis enzymes in the brain stem including hypothalamus, was investigated. The ICV injection of chicken ghrelin significantly reduced GAD₂ gene expression. These findings suggest that ghrelin may decrease food intake in neonatal chicks by reducing GABA synthesis and thereby GABA release within brain feeding centers.     

A possible mechanism of a-fluoromethylhistidine-induced increase of food intake

Inflammation Research -     

Severe reduction in food intake by pregnant rats resembles a learned food aversion

To assess the effects of sucrose, low levels of dietary protein, and pregnancy on food intake, sixty-four female rats were assigned to eight groups in a 2 X 2 X 2 design. Food, water, and sucrose intake and rats' weights were measured daily. Pregnant rats offered sucrose with low protein (8%) diets did not maintain adequate weight gain during pregnancy; 25% of these subjects perished during the last days of pregnancy. These results have implications for human populations that have high birth rates and diets that are deficient in protein. A hormonal mechanism which regulates appetite or taste preferences during pregnancy is postulated and a "learned food aversion" interpretation is given for the data.     

Evidence that wakefulness and REM sleep are controlled by a GABAergic pontine mechanism.

The pontine microinjection of the inhibitory neurotransmitter GABA and its agonist induced prolonged periods of wakefulness in unanesthetized, chronic cats. Conversely, the application of bicuculline, a GABA(A) antagonist, resulted in the occurrence of episodes of rapid eye movement (REM) sleep of long duration. Furthermore, administration of antisense oligonucleotides against glutamic acid decarboxylase (GAD) mRNA into the same area produced a significant decrease in wakefulness and an increase in REM sleep. Microinjections of glycine, another major inhibitory neurotransmitter in the CNS, and its antagonist, strychnine, did not have any effect on the behavioral states of sleep and wakefulness. These data argue forcibly that 1) GABAergic neurons play a pivotal role in determining the occurrence of both wakefulness and REM sleep and 2) the functional sequelea of inhibitory GABA actions within the pontine reticular formation are excitatory directives and/or behaviors.     

The role of drinking in the suppression of food intake by recent activity.

The standard activity-based anorexia procedure provides rats with access to a running wheel while restricting their access to dry food. This can produce reduced food intake and progressive weight loss. Using this procedure, in the present study (Experiment 1) the authors found changes in drinking patterns both in the period of high activity preceding food access and during the feeding period. Varying the procedure by providing wet mash (Experiment 2) or by prior adaptation to a drinking schedule (Experiment 3) prevented the self-starvation effect. These results indicate the importance of drinking when analyzing the effect of recent activity on food intake.     

Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.     

Cholecystokinin antagonism by benzodiazepines in the food intake in mice

Three benzodiazepines, chlordiazepoxide, diazepam and flurazepam, were demonstrated to reverse the suppressed food intake in mice in response to cholecystokinin octapeptide (CCK8). CCK8 (200 ng) was administered intracisternally, and the benzodiazepines intraperitoneally at doses of 0.1 to 1 mg/kg. The three benzodiazepines slightly depressed the feeding by themselves, but significantly reversed the satiety effects of CCK8. Naloxone (2 mg/kg) decreased the food intake but failed to reverse the CCK8 satiety action. The benzodiazepines were considered to antagonize the satiety action of CCK8 in the central nervous system through unknown mechanisms.     

Controlling the intake of calories with the intake of food

The author presents a dietary program for weight reduction based not on the substitution of a low calorie meal for a high calorie meal, but on the pre-meal ingestion of low calorie bulk beverages that are pleasant to taste and space filling, thereby compromising the capacity of the stomach to accommodate much of the higher calorie foods of the regular meals. This method makes any form of fasting unnecessary, as the intake of calories is already limited. Because of this method, few changes need to be made in food selection for regular meals.     

Carbohydrate metabolism and food intake in food-restricted rats. Relationship between the metabolic events during the meal and the degree of food intake

To study some metabolic features during feeding in food-restricted rats two groups of animals were maintained on a 2 hr feeding/22 hr fast schedule. Group D (n = 38) received a meal every day from 8:00 to 10:00 a.m. Group N (n = 34) was given the meal from 8:00 to 10:00 p.m. The average total amount of food ingested by rats of group N in the two hour period was 6.3 +/- 0.4 whereas Group D ingested 4.8 +/- 0.3 g/100 g b.w. The metabolic pattern also was different in one group as to the other. The basal liver glycogen content when feeding started was considerably lower in the nocturnal group (0.14 +/- 0.02 mg/100 mg of liver tissue) than in the diurnal group (0.44 +/- 0.10 mg/100 mg). Afterwards glycogen increased in both groups but more steeply and intensely in group N. Glycemia increased in group D and was almost invariant in group N. Insulinemia went up in both groups but in group D its peak was higher and occurred 60 minutes after the onset of feeding whereas the peak in group N was much lower and occurred at 90 minutes. There was a clear dissociation between the time courses of insulinemia and glycemia in both groups, especially in group N, which suggests a central control of insulin secretion during feeding that partially unlocks it from blood glucose concentration. The hepatic glycogen content was partially linked to the amount of food ingested but again there was a dissociation between these two variables, inasmuch as a higher glycogen replenishment in the nocturnal group corresponded to a larger food intake.     

REM sleep predicts subsequent food intake.

REM sleep time in a 12 hr period was found to predict accurately food intake in the subsequent 12 hr period in undisturbed cats fed ad lib. In all but one of the cats, the correlation between REM sleep and subsequent food intake was negative. REM sleep was a better predictor of food intake than either waking, slow wave sleep or previous food intake. Cats were then fed only during the 12 hr day period. It was found that REM sleep at night, during which no food was available, no longer predicted food intake.     

Variety in a meal enhances food intake in man

We find that in man satiety can be partly specific to foods eaten [12]. The possibility that this specificity of satiety leads to overeating if a wide variety of foods is readily available is tested here. The intakes of subjects offered a variety of foods in succession during a meal were compared to intakes when the same food was offered throughout. Subjects (n=36) ate a third more when offered sandwiches with four different fillings than when just one filling was offered (p<0.001). In another study subjects (n=24) ate significantly more when three flavors of yogurt (hazelnut, blackcurrant, orange) which were distinctive in taste, texture and color were offered than when offered just one of the flavors (p<0.01), even if the flavor was the favorite (p<0.01). However, when subjects (n=24) were offered three flavors of yogurt (strawberry, raspberry, cherry) which differed only in taste there was no enhancement of intake when the variety was offered. Having a variety of foods presented in succession during a meal enhances intake, and the more different the foods are the greater the enhancement is likely to be.     

Desensitization of GABAergic receptors as a mechanism of zolpidem-induced somnambulism

Sleepwalking is a frequently reported side effect of zolpidem which is a short-acting hypnotic drug potentiating activity of GABA_A receptors. Paradoxically, the most commonly used medications for somnambulism are benzodiazepines, especially clonazepam, which also potentiate activity of GABA_A receptors. It is proposed that zolpidem-induced sleepwalking can be explained by the desensitization of GABAergic receptors located on serotonergic neurons. According to the proposed model, the delay between desensitization of GABA receptors and a compensatory decrease in serotonin release constitutes the time window for parasomnias. The occurrence of sleepwalking depends on individual differences in receptor desensitization, autoregulation of serotonin release and drug pharmacokinetics. The proposed mechanism of interaction between GABAergic and serotonergic systems can be also relevant for zolpidem abuse and zolpidem-induced hallucinations. It is therefore suggested that special care should be taken when zolpidem is used in patients taking at the same time selective serotonin reuptake inhibitors.     

Induction of anti-idiotypic T cells through a network mechanism.

BALB/c mouse T cells that recognized the idiotype expressed on M104E(mu, lambda 1) were induced by immunization with Dextran B-1355. T cells derived from mice immunized with 1 mg of Dextran B-1355 showed a marked proliferative response against M104E, whereas T cells from mice immunized with Ficoll or smaller amounts of Dextran B-1355 did not. BCL1Id, which had an identical isotype, did not induce proliferation of T cells. The T cell proliferative response against the idiotype on M104E required macrophages as antigen-presenting cells. The proliferative response was inhibited when antigen-presenting cells were treated with NH4Cl or chloroquine, which are antigen-processing inhibitors. These results indicate that anti-idiotypic T cells which recognized processed idiotopes could be induced physiologically through a network mechanism.     

Fasting duration influences the inhibition of food intake by histamine in chickens

This work was performed to investigate the effect of duration of fasting in the responses of chickens peripherally injected with histamine on the regulation of food intake. The animals were 16-week-old male chickens from layer-strain and the doses of histamine used were 500 and 1000 microg/kg of body weight. The non fasted chickens showed no effect of histamine on the food intake. When the animals were fasted during 4 h, injected with the histamine and immediately refed, the results showed a reduction of food intake only the first 15 min of the experiments with the dose of 1000 mug. In chickens fasted during 16 h or 26 h and refed, the histamine inhibited significantly the food intake at all time with the two doses. When the animals were fasted 16 h and refed during 60 min before the administration of the histamine, there is no inhibition of food intake. No effect on water intake has been registered in all the experiments. The blockade of the action of histamine injected in chickens fasted during 16 h by cimetidine and promethazine, show that the inhibition of food intake occurs through the H1 but not through H2 receptors. The fasting used in paradigm to investigate the effect of drugs such as histamine on the appetite, can affect differently the responses according to its duration, as observed here in chickens.