Medial Hypothalamic Lesions Research Articles

Robust Reductions of Excess Weight and Hyperphagia by Beloranib in Rat Models of Genetic and Hypothalamic Obesity.

Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment-resistant obesity. We tested the methionine aminopeptidase 2-inhibitor beloranib (ZGN-440) in 2 male rat models of obesity, one modeling hypothalamic obesity with a combined medial hypothalamic lesion (CMHL) and the other modeling a monogenic form of obesity with MC4r mutations (MC4r knockout [MC4rKO]). In CMHL rats (age 3 months), postsurgery excess weight gain was significantly inhibited (ZGN-440, 0.2 ± 0.7 g/d; vehicle, 3.8 ± 0.6 g/d; P < 0.001) during 12 days of ZGN-440 treatment (0.1 mg/kg daily subcutaneously) together with a 30% reduction of daily food intake vs vehicle injection. In addition, ZGN-440 treatment improved glucose tolerance and reduced plasma insulin, and circulating levels of α-melanocyte stimulating hormone were increased. Serum lipid levels did not differ significantly in ZGN-440-treated vs vehicle-treated rats. Similar results were found in MC4rKO rats: ZGN-440 treatment (14-21 d) was associated with significant reductions of body weight gain (MC4rKO, -1.7 ± 0.6 vs 2.8 ± 0.4 g/d; lean wild-type controls, -0.7 ± 0.2 vs 1.7 ± 0.7 g/d; ZGN-440 vs vehicle, respectively), reduction of food intake (MC4rKO, -28%; lean controls, -7.5%), and insulin resistance, whereas circulating levels of interleukin-1β did not change. In both obesity models, body temperature and locomotor activity were not affected by ZGN-440 treatment. In conclusion, the robust reduction of body weight in response to ZGN-440 observed in rats with severe obesity is related to a strong reduction of food intake that is likely related to changes in the central regulation of feeding.

Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions.

BackgroundHypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. In this study, a hyperphagic rat model of combined medial hypothalamic lesions (CMHL) was used to test which specific inflammatory molecules are involved.MethodsIn order to target specific homeostatic medial hypothalamic nuclei (arcuate, ventromedial, and dorsomedial nuclei), male Sprague-Dawley rats (age of 8 weeks, ~250 g body weight) received four electrolytic lesions or sham surgery. Post-surgery food intake and weight changes were tracked and hypothalamic gene expression for inflammatory molecules as well as anorexigenic peptide oxytocin 7 days and 7 months post-surgery were tested.ResultsSeven days post-surgery, average food intake increased by 23%, and body weight gain had increased by 68%. Toll-like 4 receptor/nuclear factor–κB (TLR4/NF–κB)—pathway was specifically activated in the mediobasal hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-α, 10-fold higher interleukin (IL) 1-β mRNA levels, and higher expression of suppression of cytokine signaling (SOCS) 3, while oxytocin mRNA levels were significantly reduced in CMHL rats versus sham surgery rats 7 days post-surgery. At 7 months, inflammation was less stimulated in MBH of CMHL rats compared to 7 days post-surgery and SOCS 3 as well as oxytocin mRNA levels were comparable between the two groups.ConclusionMedial hypothalamic lesions are associated with strong post-surgery hyperphagia and activation of TLR4/NF–κB—pathway as well as reduced expression of oxytocin in the hypothalamus.

Glucagon-Like Peptide-1 Agonist Exendin-4 Leads to Reduction of Weight and Caloric Intake in a Rat Model of Hypothalamic Obesity

Background: Hypothalamic obesity caused by damage of medial hypothalamic nuclei presents a therapeutic challenge. Glucagon-like peptide-1 agonist exenatide (synthetic version of exendin-4 (Ex4)), used for treatment of diabetes, causes weight loss via hindbrain signaling. Methods: We tested Ex4 in an established rat model of medial hypothalamic lesions. Lesion and control animals were administered either daily intraperitoneal injections of 1 µg·kg^–1 Ex4 or saline for 9 days. Results: In our rat model, a significant difference in percent baseline food intake (lesion –20.8%, control –13.6%; p < 0.001) and percent change in body weight (lesion –4.9%/9 days, control –3.2%/9 days; p < 0.05) was observed during Ex4 treatment compared with saline. Conclusion: Ex4 resulted in reduction of food intake and body weight. Follow-up studies are required to further elucidate its effects on energy homeostasis and to establish Ex4 as a potential drug for treatment of hypothalamic obesity.

A Novel Rodent Model That Mimics the Metabolic Sequelae of Obese Craniopharyngioma Patients

Patients with craniopharyngioma (CP), a tumor located in the pituitary and/or hypothalamus, are susceptible to developing obesity and many metabolic complications. The study aim was to create a rodent model that mimics the complex neuroanatomical and metabolic disturbances commonly seen in obese CP patients. We compared the metabolic phenotype of animals with three distinct types of hypothalamic lesions: 1) destruction of the arcuate nucleus (ARC) induced by monosodium glutamate (MSG), 2) electrolytic lesion of the adjacent ventromedial nucleus (VMN) alone, 3) both the VMN and dorsomedial nucleus (DMN), or a 4) combined medial hypothalamic lesion (CMHL) affecting the VMN, DMN, and the ARC. Only the CMHL model exhibited all key features observed in patients with hypothalamic obesity induced by CP. These features included excessive weight gain due to increased adiposity, increased food intake, and pronounced hyperinsulinemia and hyperleptinemia. Similar to characteristics of patients with CP, CMHL animals exhibited reduced plasma levels of alpha-melanocyte stimulating hormone and reduced ambulatory activity compared with weight-matched controls. Therefore, the CMHL model best mimics the complex metabolic abnormalities observed in obese CP patients compared with lesions to other hypothalamic areas and provides a foundation for future pharmacological approaches to treat obesity in children with hypothalamic damage.

Studies of different female rat models of hypothalamic obesity

Hypothalamic obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions and is associated with hyperinsulinemia and hyperleptinemia. The purpose of this study was to create a rodent model that mimics metabolic changes in HO for use in therapeutic testing. Female Sprague-Dawley rats were used to test the individual and combined effects of two types of medial hypothalamic lesions: arcuate nucleus (ARC) lesions by injection of monosodium glutamate at neonatal age, and ventromedial nucleus (VMN) lesions by passing an anodal current through an electrode placed in the VMN at age 80 days. Adiposity in ARC-lesioned animals was associated with decreased food intake and stunted growth, while VMN lesions were associated with hyperphagia but not reduced growth. The greatest weight gain (weight at age 200 days 712 +/- 65 vs. 451 +/- 19 g in controls), hyperphagia (food intake 10 days following surgery 33 +/- 0.8 vs. 18.5 +/- 0.7 g/day in sham-treated rats), hyperinsulinemia and hyperleptinemia occurred in rats that received both ARC and VMN lesions. Thus, the combined medial hypothalamic lesions result in an obesity phenotype similar to that of patients that suffer from HO and are consequently more suitable for testing potential therapeutics for this disorder than lesions of single hypothalamic nuclei.

Hypothalamic Obesity in Patients with Craniopharyngioma: Profound Changes of Several Weight Regulatory Circuits

One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO). This drastic condition is frequently seen in patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight-regulating circuitries.

Effects of Methylphenidate on Weight Gain and Food Intake in Hypothalamic Obesity

For patients with a craniopharyngioma (CP), treatment of hypothalamic obesity (HO) and hyperphagia following resection and/or radiotherapy is extremely difficult and few reports have been published on potential drug therapies. Psychomotor stimulant methylphenidate (MPH) has been reported to inhibit food intake (FI). In this paper, we report reduction of body mass index (BMI) and appetite in an adolescent CP patient suffering from HO. We then tested the ability of MPH to attenuate the FI and body weight (BW) gain in a rat model consistent with the neuroanatomical and metabolic disturbances commonly observed in obese CP patients. Specifically, we used a novel electrolytically generated combined medial hypothalamic lesion (CMHL) affecting the arcuate nucleus, ventromedial hypothalamic nucleus, and dorsomedial hypothalamic nucleus to induce hyperphagia, rapid weight gain, and adiposity. Both CMHL and control animals (n = 7 per group) were administered either methylphenidate HCl (MPH; 20 mg kg−1 day−1) or saline for 4 days in a crossover design experiment 28 weeks post-surgery. A significant decrease in percent baseline FI (CMHL −23%, p = 0.008; control −20%, p = 0.002) and percent change in BW (CMHL −1.97%/4 days, p = 0.011; control −1.75%/4 days, p = 0.003) was observed during MPH treatment as compared to saline. Conclusion: This study shows MPH treatment of severely obese CMHL rats resulted in significantly reduced FI and BW loss.

Effects of Medial Hypothalamic Lesions on Feeding-Induced Entrainment of Locomotor Activity and Liver Per2 Expression in Per2::luc Mice

Restricted feeding induces anticipatory activity rhythm and also entrains the peripheral circadian clocks, although the underlying brain mechanisms have not been fully elucidated. The dorsomedial hypothalamus (DMH) has been implicated in the regulation of restricted feeding-induced anticipatory activity rhythms (FAA), but the role of the DMH in restricted feeding- induced entrainment of peripheral circadian clocks is still unknown. In the present study, the role of the DMH in entrainment of the peripheral circadian clock was examined using Per2::luciferase knock-in mice. The results indicate that lesions that destroy the large mediobasal hypothalamic (MBH) lesions destroying the DMH, ventrolateral hypothalamus (VMH), and arcuate nucleus (ARC) significantly reduce daily locomotor activity rhythms and FAA formation. In addition, these lesions phase advanced the peak of liver Per2 expression by 2 h when compared to sham-operated mice. Following the administration of MBH lesions, the animals run less and start later in the restricted feeding- induced FAA rhythm but do not have any alterations in the restricted feeding- induced phase shift of the liver Per2 rhythm. These results demonstrate that the hypothalamus, including the MBH, is an important brain area for maintaining the locomotor rhythm and FAA formation. However, it is not necessary for restricted feeding-induced entrainment of the liver clock.

The effect of a ventral medial hypothalamic lesion on the insulin-induced hypotensive response in normal rats.

The cardiovascular responses to insulin-induced hypoglycemia were studied in normal and ventral medial hypothalamic (VMH)-lesioned rats. The goal of this study was to investigate the role of the VMH in mediating the insulin-induced decreases in cardiovascular tone. Male Wistar rats were anesthetized with urethane/chloralose. Following the induction of anesthesia, the trachea, femoral artery, and femoral vein were cannulated. The femoral artery was attached to a pressure transducer for cardiovascular monitoring. The cardiovascular activity was recorded using a Modular Instruments Micro 5000 signal processing system. The mean arterial pressure and pulse pressures and heart rate were evaluated. In control studies, a stable plasma glucose and blood pressure were obtained with urethane/chloralose anesthesia for the duration of the experiments. Insulin (2.0 or 5.0 U/kg) significantly decreased the plasma glucose as well as the blood pressure. In VMH-lesioned rats, the lesions were accomplished by radiofrequency, and the cardiovascular response to insulin-induced hypoglycemia was investigated 1 or 6 weeks later. There was no difference in the cardiovascular response to insulin-induced hypoglycemia between the low or high insulin dose after 1 week in VMH-lesioned animals. The low dose after 6 weeks in VMH-lesioned animals did not produce a change in the mean arterial pressure response compared with controls. The pulse pressure was higher than in the sham-lesioned animals, and the plasma glucose response was greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Social condition affects the courtship behavior of male ring doves with posterior medial hypothalamic lesions

Following bilateral lesions to the posterior medial hypothalamus (homologue of the mammalian ventromedial nucleus), adult male ring doves regain full courtship behavior and the ability to stimulate female egg-laying when housed continuously with females. Males with PMH lesions housed singly and only tested periodically with females continue to show deficits in courtship. These findings suggest that the social environment present in adulthood itself can directly influence recovery from brain lesions. They also demonstrate the importance of PMH in the mediation of male ring dove courtship behavior.

Enhanced defensiveness and increased food motivation each contribute to aggression and success in food competition by rats with medial hypothalamic lesions

Castrated male rats (N = 27) with medial hypothalamic lesions or sham lesions were placed on a 23-h food-deprivation schedule and adapted to a highly palatable liquid food. They were also given two tests of defensiveness toward an experimenter. All animals were then housed in medial hypothalamic lesion/sham lesion pairs and subjected to a series of 6 competition tests (1 per day). Following the competition tests, all animals were given individual food consumption tests and a third test of defensiveness toward an experimenter. Correlational analysis showed that postcompetition defensiveness scores but not precompetition defensiveness scores or individual food consumption were related to aggression during the food competition. Analysis by criterion groups indicated that animals high in precompetition defensiveness and with food consumption in the normal range were not more successful in the competition but were slightly more aggressive than their sham-lesioned competitors. Animals with high postcompetition defensiveness scores and with individual food consumption in the normal range were more successful than their sham-lesioned competitors and the most aggressive of the lesioned animals during the food competition. Animals that were high in food consumption and only moderately defensive were also more successful but only slightly more aggressive in the food competition than their shamlesioned competitors. These results suggest that a high and stable level of defensiveness, and excessive food intake, each contribute to the success and aggressiveness of rats with medial hypothalamic lesions in a food competition situation.

Medial Hypothalamic Lesions and Sexual Receptivity in the Female Common Marmoset (Callithrix jacchus)

Medial hypothalamic lesions cause major deficits in sexual receptivity in a variety of mammalian species. Effects of such lesions upon sexual receptivity in female primates have not been investigated. Two experiments are described in which thermal lesions were made in the hypothalamus in 11 ovariectomized or ovariectomized/adrenalectomized, oestradiol-treated common marmosets. Proceptivity (sexual initiating behaviour) was reduced or abolished by lesions in the dorsomedial or ventromedial hypothalamus. Sexual receptivity was unaffected except in 3 females in which damage to the ventromedial area was associated with a 25-42% increase in terminations of males' mounts. However, this effect was reversed by treating females with oestradiol. Therefore, medial hypothalamic lesions have pronounced effects upon proceptivity in the marmoset, whereas effects upon receptivity are much less pronounced or absent. These results are discussed in relation to the evolution of the hormonal control of receptivity in anthropoid primates as compared to other mammals.

Hypothalamic effects on medullary reticular activation of deep back muscle EMG

Medullary reticular stimulation can activate deep back muscle EMG in urethane-anesthetized female rats. Midbrain central gray stimulation can facilitate brainstem reticular control over deep back muscles. Since these deep back muscles lateral longissimus (LL) and medial longissimus (ML) execute the vertebral dorsiflexion of lordosis behavior, and since the motor control hierarchy sketched above parallels lordosis behavior circuitry, we tested the hypothesis that medial hypothalamic lesions (which, in behavioral experiments, decrease lordosis) can also reduce medullary reticular activation of deep back muscle EMG. Urethane-anesthetized rats were tested systematically for amplitude of lateral longissimus (LL) and medial longissimus (ML) EMG responses to electrical stimulus trains applied to the nucleus gigantocellularis (NGC) of the medullary reticular formation, before and after electrolytic lesions of the ventromedial hypothalamus (n = 18) or control sites (n = 30). Bilateral ventromedial hypothalamic lesions were able to greatly reduce EMG responses in LL and ML, often with a time course similar to previous lordosis behavioral results. Surprisingly, lesions at the anterior ventromedial nucleus pole were particularly effective, and may reflect importance of intraventromedial local neurons. Although, on the average, various control lesions were less effective, the ventromedial hypothalamic effect was not unique. For example, it was possible to see an EMG decrease following lesions of the dorsomedial thalamus. Nevertheless, EMG loss was not well correlated with changes in the cortical EEG, and thus does not appear to be a simple consequence of changes in “arousal.” In conclusion, it appears that ventromedial hypothalamic neurons can affect medullary reticular control of back muscle EMG, but must share this role with other forebrain elements.

Female rats in a competitive situation: Medial hypothalamic lesions increase and ovariectomy decreases success and aggression

Competition for food was observed between pairs of ovariectomized female rats with medial hypothalamic lesions or sham lesions. A second series of tests observed food-competition between ovariectomized and sham-ovariectomized females. Competing pairs were continuously housed together and maintained on a 23-hr food-deprivation schedule. Competition occurred as each rat attempted to maintain access to a spout containing liquid food that only one animal could lick at a time. Female rats made hyperdefensive by medial hypothalamic lesions maintained access to a food spout significantly longer than their sham-lesioned cagemates. The lesioned animals were also significantly more aggressive than their sham-lesioned cagemates. Sham-ovariectomized rats maintained access to the food spout significantly longer than their ovariectomized cagemates. The intact cagemates were also more aggressive. These results suggest that defensive aggression heightened by medial hypothalamic lesions is displayed in a competitive situation by females as has been demonstrated previously with males. Further, ovariectomy in females appears to decrease aggression and success in a competitive situation as does gonadectomy in males. These results suggest that homologous biological mechanisms modulate aggressive behavior in male and female rats.

Intake of greasy diets in hypothalamic obesity: a re-assessment

Rats with medial hypothalamic lesions are known to prefer greasy diets. Past research has suggested that this is based on the oily texture rather than caloric content of these foods. We have re-examined this appetite in rats with bilateral parasagittal knife-cuts between the medial and lateral hypothalamus. Following knife cuts vs. sham surgery, the body weight and food consumption of adult female rats were monitored during four experimental phases. During the first month post-surgery rats were fed powdered Chow (3.61kcal/g) and showed the usual hyperphagia and obesity. Each group was then subdivided and fed either a high-fat diet (5.5kcal/g) or a similarly greasy mineral-oil diet (3.61kcal/g) for a second month. The knife-cut group fed high-fat showed significantly higher intake than both sham-cut controls and knife-cut rats fed the mineral-oil diet. The latter group showed only a non-significant feeding increase over controls. Following a third month when all groups again received Chow, animals were given the opposite greasy diet for a final month. Knife-cut rats previously fed the high-fat diet showed significant overeating of the mineral-oil diet and defended their obesity, while those fed the mineral-oil free diet first now showed significant hyperphagia and obesity on the high-fat diet. Across both target phases (months 2 and 4) knife-cut rats always ate significantly more of the high-fat diet than of the mineral-oil diet. The latter only elicited hyperphagia in animals that had been previously exposed to the high-fat diet. These findings suggest that the hyperphagic response to greasy foods relatively low in calories and digestible fats by rats with hypothalamic injury is a function of prior experience with the sensory and/or metabolic consequences of having first eaten highly caloric fatty foods. If that is true, it may be that such animals are capable of learning positive food-associated cues in addition to negative ones (i.e. enhanced taste aversions) documented earlier by other investigators.

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. In a second experiment a unilateral far-LH lesion decreased both feeding and contralateral perifornical LH self-stimulation. In Experiment 3, 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. These results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, the results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. In all three experiments LH self-stimulation and food intake covaried, which suggests that they are functionally related.

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

Lateral and medial hypothalamic lesions do not acutely affect brown adipose tissue thermogenesis

The acute effect of lateral (LH) and medial (MH) hypothalamic lesions on mitochondrial GDP binding in brown adipose tissue (BAT) (an index of thermogenic state) was studied one and two days postlesion. Groups of rats were lesioned, sham-lesioned, or unoperated and were all fasting. An additional group of unoperated rats had access to food throughout the study. The objective was to determine whether the hypermetabolic state and rapid weight loss known to be induced by LH lesions were attributable to the activation of BAT thermogenesis, and, if so, whether these effects were specific for LH lesions. No effect of either lesion on BAT thermogenic state could be detected at either time studied. Despite that fact, LH-lesioned rats, but not MH-lesioned rats, were hyperthermic at both times. We conclude that the prolonged hyperthermia which occurs shortly after LH lesions is not due to an activation of BAT thermogenesis. Instead, it can be likened to the febrile state in which an initial and brief activation of both nonshivering thermogenesis in BAT and shivering thermogenesis in muscles occurs only during the rising phase of the fever and is suppressed as soon as a stable hyperthermic state is reached. It thus appears unlikely that substantial and prolonged activation of BAT thermogenesis is a major mechanism that promotes exaggerated short-term weight loss in the LH-lesioned rat.

Defensive aggression and testosterone-dependent intermale social aggression are each elicited by food competition

Castrated rats with medial hypothalamic lesions or sham lesions and castrated rats with testosterone implants or sham implants were placed on a 23-hr food deprivation schedule, adapted to a highly palatable liquid food, and then housed in pairs. The pairs were observed in competition for the highly palatable food over a 4-min period on each of six days. On the first three days, the food was dispensed in a way that allowed only one animal at a time to drink while during the second three days both animals could drink simultaneously. The pairs of animals were then separated, individually adapted to a bland liquid food, and paired with a different animal for a second series of competition tests. With highly palatable food as the incentive, rats made hyperdefensive by medial hypothalamic lesions were more successful at maintaining access to the food and more aggressive than their sham-lesioned competitors on tests when food access was restricted to a single animal but not on tests when both animals could drink simultaneously. With bland food as the incentive, lesioned animals were not consistently more successful in maintaining access to the food but were significantly more aggressive than their cagemates. With the highly palatable food, castrated males with testosterone implants were neither more successful in maintaining access to the food nor more aggressive than their cagemates with sham implants. However, when paired with an unfamiliar cagemate in preparation for competition tests with the bland food, most rats with testosterone implants attacked the new cagemate using a lateral attack and displaying piloerection. During the competition tests, the animals with testosterone were both slightly more aggressive and slightly more successful in maintaining access to the food than their cagemates with sham implants. In contrast to rats with lesions, once aggression appeared in animals with testosterone implants, it was used to monopolize access to food even when the physical conditions permitted sharing. These findings are consistent with previous observations indicating that both defensive and testosterone-dependent aggression can be elicited by a competitive situtation.

Competitive behavior: Intact male rats but not hyperdefensive males with medial hypothalamic lesions share water with females

Male hooded rats with medial hypothalamic lesions or sham lesions were given tests of defensiveness toward an experimenter. The 8 lesioned males with the highest defensiveness scores and 7 sham-lesioned males were each placed in a double cage with a single intact female. For each pair of rats, food was continuously present but water was available for only 1 hr/day through a single water spout. Beginning on the fifth day of water deprivation, each pair of animals was given a 4-min water competition test on 3 consecutive days. Competition for water was created by placing a plastic ring over the hole in the cage where the water spout entered the cage. The ring restricted access to the spout to a single animal and was put in place 5 min before water was given. One hr following the competition test, each pair of animals was given access to a single unencumbered spout for a 1-hr period. Rats with medial hypothalamic lesions drank significantly more and initated more aggression than their female cagemates during the 4-min competition tests. Sham-lesioned rats neither drank significantly more nor were more aggressive than their female cagemates. These results are consistent with previous observations indicating that the aggressiveness of rats with medial hypothalamic lesions can be elicited by a competition situation.