Reactivity to food odors during hypothalamic stimulation in rats not experienced with stimulation-induced eating

Rats were given tests which permitted access to food-related or water-related stimuli, but which prevented the opportunity to eat or drink. The rats appeared attracted to odors or other stimuli associated with food when they were deprived of food and water for 23 hr. The rats were not attracted to the food stimuli when they were undeprived nor when they were subjected to electrical stimulation of the lateral hypothalamus at an intensity which induced eating in later tests. If the rats were given the same brain stimulation when food and water deprived, they appeared attracted to the food stimuli. After finally permitting access to food and water during stimulation, it was found that those rats which became stimulation-induced eaters had not differed from the noneaters/drinkers on any of the prior tests, but that in later tests only the eaters readily approached food stimuli. The different behaviors of the eaters and noneaters did not appear to be attributable to emotional factors as previously suggested by others. The results are discussed in terms of both nonspecific arousal factors and specific hypothalamic contributions to stimulation-induced ingestive behaviors.     

Feeding rate and responses to food deprivation as a function of fasting-induced hypoglycemia

The relation between hypoglycemia induced by 3 hr of food removal at various times throughout the day and the amount eaten during the corresponding ad-lib periods was examined in rats. It was found that the 3-hr-deprivation fall in blood glucose was different between the night and the daytime and also between the beginning and the end of the daytime. A highly significant correlation existed between the 3-hr ad-lib intake and this time-dependent fall in blood glucose. Moreover, the correlation between the same fall in blood glucose and increases in subsequent intakes after 3-hr deprivation was also significant. The conclusion is drawn that rats eat at a rate just required to prevent hypoglycemia under ad-lib conditions and that after food deprivation they transiently increase this rate to correct the fall in blood glucose and to reestablish the required supply of glucose to tissues.     

Effects of lateral hypothalamic lesions on food intake of rats during exposure to cold

Lateral hypothalamic damage impaired both physiological and behavioral responses of rats during exposure to a 5 degree C environment. The brain-damaged animals usually did not conserve heat in the cold as well as control rats did, nor did they always increase their caloric intake to meet their energy needs. However, when given sucrose solution to drink instead of water, they did increase their ingestion of chow in response to cold exposure. It is likely that the elevated consumption of palatable fluid served to relieve dehydration and thereby removed its constraints on eating, thus permitting hyperphagia to occur. In contrast to these results, rats with large dopamine-depleting brain lesions, produced by intraventricular 6-hydroxydopamine treatments, always increased food intake when exposed to cold stress and demonstrated no apparent problems in peripheral vasoconstriction. Thus, it is unlikely that striatal dopamine depletions account for either the impaired feeding response or the inadequate heat conservation of rats with lateral hypothalamic lesions during cold stress.     

Effectiveness of lateral hypothalamic stimulation, arousal, and food deprivation in the initiation of hoarding behaviour in naive rats

Hoarding behaviour was elicited by electrical stimulation of points in the lateral hypothalamus which also supported stimulus-bound feeding, even in animals which had never hoarded before. Electrical stimulation was not quite as effective as 16-hr food deprivation. Hoarding was not induced by stimulation of other hypothalamic sites, including sites where stimulation caused increased locomotor activity or self-stimulation. Thus increased arousal, or reinforcing effects in the presence of goal objects are not a sufficient condition for the appearance of a goal-directed behaviour such as hoarding.     

Monkey lateral hypothalamic neuron response to sight of food,and during bar press and ingestion

Unit activity of 144 lateral hypothalamus (LHA) neurons was analyzed in monkey during bar pressing feeding behavior. Eighteen neurons responded only when the animal saw food, and 23 responded only during ingestion of food. Ten responded at both the sight of food and throughout the bar pressing and ingestion periods, even in high fixed ratio schedules. Three neurons responded, not at the sight of food, but at the sight of non-food. Nineteen out of a total of 54 of the above responding neurons were studied for response to differences between food and non-food. Eight responded similarly at the sight of both food and non-food, while 11 responded differently. Responses during the ingestion period were strong and lasted longer than 5–10 sec. The data indicate that some LHA neurons are involved in the discrimination of food, the drive to obtain it and the perception of reward.     

Monoamine metabolism and its responses to food deprivation in the brain of Zucker rats

Monoamines and their metabolites levels were simultaneously measured by high-performance liquid chromatography in brain regions of lean and fatty Zucker rats when fed ad lib and deprived of food for 72 hr to evaluate each monoamine metabolism. Metabolite/monoamine ratios were shown for brevity to represent its metabolism. 3-Methoxy-4-hydroxyphenylethyleneglycol/noradrenaline ratios were not affected by the phenotype factor but increased in the cortex of fatty rats and reduced in the midbrain of both phenotypes after fasting; the interaction between phenotype and feeding factors was observed in the cortex and hippocampus. 3,4-Dihydroxyphenylacetic acid/dopamine ratios were increased in the cortex of deprived fatty rats and in the medulla-pons of ad lib-fed fatties compared with lean counterparts and also increased in the striatum of lean rats after food deprivation; the interaction was observed in the cortex, midbrain and medulla-pons. Homovanillic acid/dopamine ratios were decreased in the striatum of deprived fatty rats and in the midbrain and medulla-pons of fatty rats whether deprived or not, but the ratios were not significantly changed by fasting; the interaction was observed in the striatum. 5-Hydroxyindoleacetic acid/5-hydroxytryptamine ratios were reduced in the cortex, striatum and medulla-pons of fatty rats in both feeding states and in the midbrain of deprived fatties, and after food deprivation increased in the cortex and midbrain of lean rats and in the hippocampus of both phenotypes; the interaction was observed in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of rat lateral hypothalamic neuron activity to dorsal raphe nuclei stimulation

1. The effects of dorsal raphe (DR) stimulation on neural activity in the rat lateral hypothalamic area (LHA), including specific glucose-sensitive neurons, were investigated by extracellular and intracellular recording in vivo, and the neurotransmitters involved were determined. 2. In 67 adult male anesthetized rats, 287 extracellular and 49 intracellular recordings of LHA responses to electrical stimulation of the DR were examined. 3. To determine neurotransmitter candidates, the effects of serotonin and the serotonin antagonists methysergide, lisuride, and (-)-propranolol were investigated by systemic administration and microelectrophoresis. 4. Of 287 spontaneously firing LHA neurons tested by DR stimulation, 157 (55%) were inhibited. Among these, 51% were glucose sensitive. The serotonin 1 receptor antagonists, lisuride and (-)-propranolol, attenuated the inhibitory responses to both DR stimulation and electrophoretic serotonin application. 5. Seventy-three (25%) were excited by DR stimulation, and 71% of these were glucose insensitive. Methysergide attenuated the excitatory responses to DR stimulation and the inhibitory response to electrophoretic serotonin application, but (-)-propranolol did not attenuate the excitation. 6. Intracellular recordings of LHA neurons during DR stimulation showed monosynaptic excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) with 3.8 and 3.0 ms latency, respectively. The reversal potential for the former was approximately -17 and for the latter, -94 mV. 7. From the results we concluded that 75% of LHA glucose-sensitive neurons receive inhibitory serotonin inputs from the DR through serotonin 1 receptors, and 20% of glucose-insensitive neurons receive excitatory inputs from the DR through serotonin 2 receptors though 41% of these receive inhibitory inputs through serotonin 1 receptor.     

Feeding pattern in Peromyscus maniculatus: The response to periodic food deprivation

The prairie deermouse (Peromyscus maniculatus bairdi) is strongly nocturnal on a 12:12 LD-cycle with a bimodal, dusk-dawn feeding pattern. It has been suggested for the rat that the dusk peak is more dependent on the animal's immediate energy needs while the dawn peak has an anticipatory function in storing food. The present study investigates this pattern in terms of the feeding response of deermice following periodic food deprivation. It was found that the response is not uniform within the D-phase; survivability, food intake, and maintenance of body mass were all favored by access to food during the final six hours vs the initial six hours. Deprivation experience enhanced survivability with the early-food, presumably through a reduction in locomotor activity and not by increased food intake. These results suggest a rigid temporal organization of feeding behaviors whereby early-night foraging and hoarding are necessary in allowing for late-night filling in anticipation of the L-phase.     

Spontaneous mouse killing rats: gentling and food deprivation result in killing behavior almost identical to that of rats with medial hypothalamic lesions

Rats that were found to kill a mouse spontaneously were divided into two groups. One group was left untreated and allowed free access to food while the other was gentled for 15 min/day and given only 15 g of food/day. Nonkilling rats were induced to kill mice by lesions of the medial hypothalamus. Seven to ten days after being divided into groups or subjected to brain lesions, each rat's behavior toward a series of stimuli was observed. The stimuli were a live mouse, a second live mouse, a freshly killed mouse, and a cotton wad. Food-deprived/gentled spontaneous killers and rats induced to kill by medial hypothalamic lesions each tended to attack with higher intensities and lower latencies than control spontaneous killers. The food-deprived/gentled spontaneous killers and lesion-induced killers (but not the control spontaneous killers) also attacked a dead prey moved vertically and then held onto the prey with sufficient intensity that their feet would leave the floor of the cage before they would release their grip on the prey. It is argued that the behavior of food-deprived spontaneous killers may constitute a more valid model of spontaneous mouse killing than that of sated spontaneous killers. The close correspondence between behavior toward a prey by lesion-induced killers and food-deprived spontaneous killers suggests that the lesion-induced killers fit this model of mouse killing remarkably well.     

Noradrenaline-induced feeding responses in the rat do not depend on food characteristics

The noradrenergic system of the hypothalamic paraventricular nuclei (PVN) has been associated with feeding, but whether it controls feeding in a way that is relevant to energy balance is still unclear. Rats were maintained on a high energy, carbohydrate-rich diet (HC) or a low energy, carbohydrate-free, protein-rich diet (LP) until their daily energy intakes equalized. When injected with noradrenaline (NA) into the PVN, they ingested the same amounts of both diets so that the animals on the LP diet consumed only half the total energy of those on the HC diet. Continuous delivery of NA into the PVN via a microdialysis probe induced chewing on non-nutritive pieces of corks. The same chewing pattern could again be elicited by the subsequent NA deliveries. It is concluded that the nutritional value of a diet is irrelevant to the NA feeding response. The failure of NA administration to increase rat feeding in terms of energy intake, combined with its ability to stimulate chewing, suggests that the primary role of the NA system of the PVN may not be controlling the carbohydrate and energy intake, but rather gating behavioral responses that under appropriate circumstances may lead to ingestion.     

Feeding behavior responses of Zucker rats to naloxone

The effects of naloxone on feeding patterns were studied in both obese and lean Zucker rats during both light and dark phases of the diurnal cycle. Eight female obese (471±9 g) and lean (225±6 g) Zucker rats were trained to bar press for food. They were administered 0, 0.5, 1.0 or 2.0 mg/kg naloxone at the initiation of the light or dark phase of the diurnal cycle and feeding behavior was recorded for the subsequent 12 hr using an automated real-time data collection system. First meal size and duration were decreased and first postmeal interval was increased by naloxone and responses did not vary with phenotype or phase of the diurnal cycle. Naloxone decreased food intake during the 12-hr period by decreasing average meal size but meal frequency was not affected. Overall, the feeding behavior responses of obese rats to naloxone were greater than those of lean rats, supporting the hypothesis of an association between opioid peptides and obesity. Opioid involvement in diurnal control of food intake is also supported by the greater responses generally demonstrated in the light compared with dark phases.     

Digestibility in male rats with lateral hypothalamic lesions

The body weight of male rats with lateral hypothalamic lesions remained approximately 20% below that maintained by nonlesioned controls. One month following surgery, both food intake and energy losses in feces and urine were measured in all animals for five days. The percentage of ingested food absorbed by the gut (“digestibility”) was determined from calorimetric analysis of the feces to be slightly, though significantly, higher for the lesioned animals (79.7% vs 77.4%). Resorptive capacity, as indicated by the percentage of absorbed energy lost in the urine, was determined to be the same for the lesioned and control animals (4.8% vs 4.5%). These results indicate that the digestive, absorptive, and resorptive processes of LH-lesioned animals are at least as efficient as those of nonlesioned animals maintaining normal body weights. Thus, though LH-lesioned animals are reported to display various gastrointestinal dysfunctions, alterations in digestive or resorptive efficiency are apparently not responsible for their chronically-reduced body weights.     

Glutamate and GABA in lateral hypothalamic mechanisms controlling food intake

By the 1990s a convergence of evidence had accumulated to suggest that neurons within the lateral hypothalamus (LH) play important roles in the stimulation of feeding behavior. However, there was little direct evidence demonstrating that neurotransmitters in the LH could, like electrical stimulation, elicit feeding in satiated animals. The present paper is a brief review in honor of Bartley Hoebel's scientific contributions, emphasizing the evidence from my lab that the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in the LH mediate feeding stimulation and feeding inhibition respectively. Specifically, we summarize evidence that LH injection of glutamate, or agonists of its N-methyl-d-aspartate (NMDA) and non-NMDA receptors, elicits feeding in satiated rats, that NMDA receptor antagonists block the eating elicited by NMDA and, more importantly, that NMDA blockade suppresses natural feeding and can reduce body weight. Conversely, GABA_A agonists injected into the LH suppress feeding and can also reduce body weight, while GABA_A receptor antagonists actually elicit eating when injected into the LH of satiated rats. It is suggested that natural feeding may reflect the moment-to-moment balance in the activity of glutamate and GABA within the LH.     

Head displacement and bracing in haloperidol-treated rats compared to rats with lateral hypothalamic damage

A characteristic of catecholamine-depletion-induced catalepsy is that such animals resist horizontal displacement, forward, backward or sideward, by bracing, i.e., pushing against the displacing force rather than stepping away as do normal animals. In this report the bracing responses of two cataleptic preparations were compared: (1) intact rats given haloperidol, a dopamine antagonist, and (2) rats with large lesions of the lateral hypothalamus (LH). Although both preparations exhibited exaggerated bracing responses when pushed, the LH rats acted in a non-cataleptic manner when pushed backward by the head; they retreated backward. The backward walking was a head-elicited response, because pushing the body backwards by the shoulders elicited bracing, not walking. Other forms of head displacement elicited body bracing if the body's stability was challenged: as when the head (and thus the body) was pulled forward; or no strong bracing responses if the head was displaced without affecting the body's stability, i.e., when as the head was pushed laterally. Therefore, retreating rather than bracing was elicited by one specific form of head displacement: backward. In contrast, haloperidol-treated rats braced whenever the body's stability was challenged, including when the head was pushed backward.     

Response to acute food deprivation in OLETF rats lacking CCK-A receptors

Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking cholecystokinin (CCK)-A receptors are hyperphagic and obese, and exhibit deficits in meal size control and in neuropeptide Y (NPY) gene expression in the dorsomedial hypothalamus (DMH). The present study was intended to determine whether these deficits would affect OLETF rat's response to an acute 24-h period of food deprivation. OLETF rats lost more body weight in response to deprivation but recovered their weight more quickly during refeeding than did lean Long-Evans Tokushima Otsuka (LETO) rats. Food deprivation decreased plasma glucose and leptin levels to a similar degree in both strains. Both groups increased intake during refeeding but the magnitude of increase was significantly greater in OLETF rats. Deprivation resulted in a significant elevation in arcuate NPY gene expression (approximately 47%) in LETO rats but only produced a small nonsignificant increase in the already decreased level of expression in OLETF rats (approximately 24%, P>.05). DMH NPY gene expression was not changed by deprivation in either OLETF or LETO rats. Although paraventricular corticotropin-releasing factor (CRF) expression was decreased by deprivation in LETO rats, CRF expression was not affected in OLETF rats. Together, these data suggested that OLETF rats lacking CCK-A receptors are not only capable of increasing their food intake in response to food deprivation, but also exhibit differential sensitivity to the effects of deprivation during both the food deprivation and refeeding periods.