Lateral hypothalamic stimulation: Stimulus-bound eating and self-deprivation

Research was undertaken in an attempt to clarify the relationship between stimulus-bound eating and self-deprivation produced by electrical stimulation of the lateral hypothalamus. It was hypothesized that if these two phenomena are mediated through a common population of feeding-related neurons, a significant correlation should be observed between these two behaviors. No significant relationship was discovered among the rats tested for both stimulus-bound eating and self-deprivation. Although this finding by itself does not rule out some role for feeding-related neural elements in stimulus-bound eating and self-deprivation, the present results provide no support for this view and suggest alternative explanations should be sought.     

Re-emergence of hypothalamically elicited eating following change in food

Rats with lateral hypothalamic electrodes were administered electrical stimulation until the elicited eating of one type of food had emerged to asymptotic levels. Experimental animals later were presented with a different diet, and elicited eating underwent another emergence process. This re-emergence occurred despite the fact that animals had had deprivation experience with the second food immediately prior to stimulation experience with it. These data present interpretative difficulties for the hypothesis that elicited behavior reflects the activation of neural systems underlying deprivation-induced consummatory activity and that the anomalous characteristics of elicited responding can be attributed to an emotionality state which theoretically is also evoked by the stimulation.     

Effects of cortical spreading depression on behaviors elicited by hypothalamic stimulation in rats

Eating or drinking was elicited via electrical stimulation of the lateral hypothalamus of rats. To determine the effects of single waves of cortical spreading depression on elicited behavior, 1,1 animals were tested with 10 sec trains of stimulation at 20 sec intervals and administered 1–5 μl of 6% KCl through cannulae onto the frontal or occipital cortices of the contralateral or ipsilateral hemispheres. Under single waves of bilateral spreading depression the elicited consummatory behavior was blocked, but other signs of arousal were intact. Single waves of unilateral depression increased the onset-latencies and decreased the duration of elicited behavior, depending on the magnitude of the electrical stimulation. Anterior cortical injection blocked elicited behavior earlier than occipital injection. No differences were apparent between ipsilateral and contralateral injection of KCl. In some animals single waves of unilateral depression were accompanied by a reversible shifting from one elicited consummatory response to another, usually from eating to drinking. The results were interpreted to reflect cortico-hypothalamic interactions in the control of motivated behavior.     

Neurogenic non-adrenergic cutaneous vasodilatation elicited by hypothalamic thermal stimulation in dogs

Hypothalamic heating in dogs with depleted peripheral adrenergic transmitter stores by means of chronic application of reserpine elicits increase of hindpaw blood flow. The vasodilator response is not affected by alpha- and beta-adrenergic or cholinergic blocking substances, nor by histamine-, or prostaglandin-antagonists. Dopamine and ergometrine produce cutaneous vasoconstriction which is antagonized or prevented by haloperidol. The hypothalamic vasodilator response is abolished after intra-arterial injection of haloperidol, after lumbar sympathetic chain section, or by high doses of hexamethonium. The results indicate neurogenic non-adrenergic control of skin blood flow in thermoregulation possibly acting through inhibition of dopaminergic vasoconstrictor mechanisms.     

Strain differences in eating and drinking evoked by electrical stimulation of the hypothalamus

Electrical stimulation of the lateral hypothalamus (ESLH) has been shown to produce individual response differences that cannot be attributed to the neuroanatomical locus of the electrode. The purpose of the present experiment was to investigate strain differences in the incidence of eating and drinking evoked by ESLH. The responses of 49 Long-Evans and 51 Sprague-Dawley male rats implanted with bilateral hypothalamic electrodes were studied. Animals from these two strains do not differ in their normal food or water consumption. Analysis of the responses to ESLH demonstrated that a significantly greater number of Long-Evans rats ate food and/or drank water during ESLH than did the Sprague-Dawley rats. These results could not be attributed to differences in electrode placements, or rearing conditions. In addition to strain differences, the importance of individual differences within each strain was demonstrated by the fact that both electrodes in a given animal commonly evoked the same behavior. Hypotheses to explain these results are discussed.     

The effects of ambient and hypothalamic temperatures on the hyperthermic responses to prostaglandins E1 and E2

Summary The effects of ambient and hypothalamic temperatures were studied on the hyperthermic responses to prostaglandins E₁ and E₂ (PGE₁ and PGE₂) injected intraventricularly in the unanesthetized rabbit. Hyperthermic responses to PGE₁ observed at different thermal environments were approximately equal in magnitude and time course. However, the prevailing ambient temperature influenced the thermoregulatory mechanisms by which the hyperthermia was achieved. In a hot environment, PGE₁-hyperthermia was brought about by suppression of heat loss mechanism with little change in heat production. During cold exposure body temperature was raised mainly by an increase in heat production without a significant change in heat loss. PGEs-hyperthermias were attenuated by warming and enhanced by cooling the anterior hypothalamus. These changes in the hyperthermic responses to PGE₁ and PGE₂ are in contrast to those obtained with intraventricular injection of noradrenaline at different ambient temperatures and during hypothalamic heating and cooling. It is therefore unlikely that noradrenaline is involved in the hyperthermic responses to PGEs. On the other hand, the results support the view that prostaglandins may be mediators of pyrogen-induced fever.     

Modulation of hypothalamic ICSS by concurrent limbic stimulation

Four rhesus monkeys were surgically implanted with arrays of subcortical electrodes and trained to self-administer rewarding electrical stimulation (ICSS) to the hypothalamus. In all four animals, concurrent electrical stimulation of the CA3 region of uncal anterior hippocampus or of the cortico-medial region of amygdala inhibited hypothalamic ICSS. In two of the four animals, concurrent stimulation of the more posterior hippocampus (CA3) facilitated ICSS. Concurrent stimulation of other areas (including basolateral amygdala, hippocampal CA4 region, internal capsule, optic tract, thalamus, and caudate nucleus) had no effect on hypothalamic ICSS. It is suggested that hypothalamic reinforcement processes may vary according to the parameters of limbic involvement.     

Effects of hypothalamic deafferentations on adrenocortical responses in the rat following hippocampal stimulation

Summary Adrenocortical responses, as expressed by changes in plasma corticosterone levels, following ether stress and dorsal hippocampal stimulation, were studied in intact rats and in rats with complete, anterior or posterior hypothalamic deafferentations. Ether stress produced normal responses in all experimental groups. In the three groups with hypothalamic deafferentations, the adrenocortical response following hippocampal stimulation was completely blocked, when compared to intact animals. The results suggest that the hippocampal signal enters the hypothalamus anteriorly, but that caudal propagation and posterior re-entry into the hypothalamus are also essential for the adrenocortical activation by the hippocampus.Supported by US-Israel Binational Foundation grant 1554/78     

The control exerted by the substantia nigra on the quiet biting attack elicited by hypothalamic stimulation in the cat

The effects of substantia nigra (SN) (pars compacta) stimulation on the quiet biting attack evoked by hypothalamic activation in the cat were studied. The measure of the aggressive behavior was the latency of the biting which did not greatly change from one animal to another when hypothalamic stimulation was performed with the same parameters. Concurrent activation of the SN determined an inhibitory effect on the studied behavior in the form of an increase in the biting latency or loss of the attack pattern. The inhibitory role of the SN on predatory attack behavior is discussed.     

Effect of exercise on energy intake and eating patterns in lean and obese humans

Twelve obese and four lean subjects increased their energy expenditure by 100 kcal/day by cycling on a bicycle ergometer. The order of testing was alternated so that half of the subjects did exercise on the first three days and the remainder on the last three days. Ad lib energy intake was measured over six days using an automated food dispensing machine. The obese subjects ate 1196±517 kcal/day and the lean subjects ate 1162±301 kcal/day and showed no overall significant difference in energy intake or eating patterns. However, these obese subjects ate 18 kcal/day less and the lean subjects ate 155 kcal/day more during the exercise period. The difference in response confirms the hypothesis that lean subjects tend to regulate energy intake more accurately than obese subjects. Exercise increased the frequency of eating and drinking and decreased hunger and appetite for all subjects. There was a significantly greater decrease in hunger and appetite with exercise for the obese subjects. However, as there was no accompanying decrease in energy intake and some subjects had difficulty in completing the exercise, the value of small increases in voluntary exercise in the treatment of obesity is questioned.     

Forelimb and hindlimb stepping by the anesthetized rat elicited by electrical stimulation of the diencephalon and mesencephalon

Thirty rats anesthetized with a combination of chloralose, urethane and nembutal or nembutal alone were fixed in a stereotaxic apparatus and suspended over a moving treadmill belt. Electrical stimulation (100 microA, 10-sec trains, 0.5-msec cathodal pulses, 50-Hz pulse frequency) was applied every 200-microns through 109 movable electrodes. The patterns of stepping elicited ranged from well-coordinated stepping of all four limbs to spastic stepping of only one limb. In the hypothalamus, stepping-positive sites were found in and dorsal to the medial forebrain bundle, the paraventricular, dorsomedial and posterior nuclei, and the supramammillary areas. Dorsally, effective regions extended to the medial zona incerta and the fields of Forel. In the thalamus only the parafascicular nucleus and the anterior parts of the rhomboid and reuniens nuclei were positive. Positive sites were particularly dense in the ventral tegmental area. In the dorsal midbrain positive sites were most common at caudal levels dorsal and dorsolateral to the central gray. At sites in the area of the medial raphe, stepping was elicited only at the offset of the train. The distribution of positive sites resembled that found in unanesthetized rats and indicates that pathways at which electrical stimulation elicits stepping are separated into dorsal and ventral systems at the level of the midbrain.     

The effects of overfeeding and propensity to weight gain on the neuronal responses to visual food cues

Obesity is a serious and growing public health problem in the United States and the world. The pathophysiological processes that underlie the increasing prevalence of obesity have not been clearly defined but likely involve faulty interactions between environmental factors, which favor positive energy balance, and weight regulatory systems in genetically susceptible individuals. Individuals who are genetically predisposed to thinness in the current environment may be able to sense and respond to excess energy intake more rapidly and accurately than those predisposed to obesity. The regulation of energy intake and therefore the potential adaptation to changes in energy balance is a complex process with interactions between homeostatic and non-homeostatic signals likely being critical. We have observed that thin (obese-resistant) individuals quickly sense changes in positive energy balance with not only changes in measures of appetite but also in brain regions important for the regulation of energy intake. This is in contrast to reduced-obese (obese-prone) individuals who do not appear to appropriately sense the changes in positive energy balance, suggesting that there is a differential sensitivity to positive energy balance between obese-resistant and obese-prone individuals. We have also found evidence for important interactions between external food cues and activation of brain regions important in the homeostatic regulation of energy balance. These findings emphasize the important role of environmental visual cues and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions important in the regulation of energy intake.     

The effect of hypothalamic stimulation on the growth transplanted sarcomas

Summary Hypothalamic stimulation repeated many times over a long period in albino rats produced one of two different effects on the growth of grafted 45 and M-1 sarcomas. If the stimulation preceded the transplantation, the growth of the tumor was suppressed, and the tumor might even be completely absorbed. If stimulation followed the transplantation, tumor growth was intensified. A number of hypothalamic nervous structures were involved.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny Vol. 53, No. 5, pp. 111–116, May, 1962     

Effects of sodium acetylsalicylate on thermoregulatory responses of rats to different ambient temperatures

The effects of intraperitoneal administration of sodium acetylsalicylate (aspirin) on thermoregulatory responses (T_a) of 15, 22 and 29°C were assessed. Intraperitoneal administration of aspirin produced dose-dependent hypothermia at both 15 and 22°C. The hypothermia was brought about by cutaneous vasodilation (as indicated by an increase of the tail and foot skin temperatures). However, in the heat (29°C), i. p. administration of the same amount of aspirin produced no change in rectal temperature, since the thermoregulatory responses were unaffected by aspirin application at this T_a. Thus it appears that aspirin increases heat loss and leads to hypothermia in rats.     

The effect of electrical stimulation of the hypothalamus on continuously-monitored blood glucose levels

The effects of hypothalamic stimulation on blood glucose levels were investigated in unanaesthetised rats with intracardiac catheters directly connected to a continuous glucose analyzer. Thirty sec of low level electrical stimulation produced hyperglycemia at 23 of the 34 sites stimulated. At the remaining 11 sites the electrical stimulation produced no changes in blood glucose levels. The hyperglycemia could be dissociated from the changes in motor activity produced by the stimulation. The highest probability of producing hyperglycemia was found at ventro-lateral sites although hyperglycemia was also observed after stimulation of dorsal and medial sites. Apart from this medio-lateral difference in the density of sites at which stimulation produced hyperglycemia, the effects were not well differentiated anatomically. In addition, in terms of latency, peak magnitude and duration of the hyperglycemia, stimulation of the various hypothalamic subdivisions appeared to be functionally equivalent. Thus with respect to hypothalamic involvement in the maintenance of blood glucose levels the present stimulation analysis suggests a medio-lateral functional similarity which is very different from the medio-lateral reciprocity of lesion effects on ingestive behaviour and body weight.     

The effect of isoflurane and halothane on electroencephalographic activation elicited by repetitive noxious c-fiber stimulation

Windup is the progressive increase in neuronal response to a repetitive noxious stimulus. This response is most often observed in the spinal cord, but it is unclear how this response is manifested in supraspinal structures. We investigated the effects of isoflurane and halothane on electroencephalographic responses to repetitive noxious electrical stimuli (20 pulses at 0.1, 1 and 3 Hz) applied to the tail in rats. Halothane and isoflurane concentrations were adjusted to 0.8 and 1.2 minimum alveolar concentration (MAC), where MAC is the concentration needed to prevent gross and purposeful movement in 50% of animals. At 0.8 MAC halothane, the 3 Hz stimulus caused electroencephalographic (EEG) activation primarily by increasing the median edge frequency (MEF), while at 1.2 MAC halothane the spectral edge frequency (SEF) was increased by the 1 and 3 Hz stimuli, and the MEF was increased by the 3 Hz stimuli. At 0.8 MAC isoflurane, the 1 and 3 Hz stimuli evoked EEG activation by increasing the MEF and SEF, while at 1.2 MAC only the MEF was increased by the 1 Hz stimulus. No EEG activation occurred with the 0.1 Hz repetitive stimulus with either isoflurane or halothane. These data suggest that repetitive electrical stimulation normally associated with windup in spinal neurons can evoke EEG activation.     

Effects of sciatic nerve stimulation on ACTH secretion,in intact and in variously hypothalamic deafferentated male rats

Summary Serum ACTH levels were determined by RIA following sciatic nerve stimulation, in intact rats and in rats bearing anterior (AHD), posterior (PHD) or complete (CHD) hypothalamic deafferentations. In both N and PHD groups, serum ACTH concentrations were markedly elevated following stimulation. In CHD animals this response was completely eliminated, and in the AHD group only a very slight and marginally significant increase in serum ACTH occured, upon stimulation. These results demonstrate that the increased corticosterone secretion which occurs following sciatic nerve stimulation is due to elevated blood levels of ACTH, and confirm that this somatosensory stimulation impinges upon the hypothalamus from the rostral directions.Supported by the US-Israel Binational Foundation grant 1554/78     

The effects of lactation and ambient temperature on the body temperature of female Norway rats

Norway rat dams were placed in an ambient temperature of 4°C, 22°C, or 28°C. Body temperatures were recorded over a two hour period on three days; each female was observed on Day 4 and Day 10 of lactation and three days after lactation was stopped. Body temperatures were initially higher during lactation than after lactation had stopped. Dams were less able to maintain their body temperatures in the 28°C ambience on Day 4 of lactation than after lactation, and on Day 10 of lactation, were even less able to maintain their body temperatures than on Day 4. During lactation, dams were able to maintain and even increase their body temperatures in the 4°C ambience. The data support the hypothesis that the acute hyperthermia encountered by rat dams during contact with their litters may be due to a physical restriction on maternal heat loss.