Meal patterns of rats with dorsomedial hypothalamic nuclei lesions or sham operations

Rats with bilateral dorsomedial hypothalamic electrolytic lesions (DMNL rats) are hypophagic, hypodipsic and have reduced linear and ponderal growth when compared to sham operated controls (SCON). Nevertheless, previous studies have shown that DMNL rats eat and drink adequate amounts for their size and have normal body composition. In the present study we investigated meal parameters: meal size, and frequency (both light and dark period), total intake and meal size per metabolic size (body weight 0.75). Compared to SCON, DMNL rats at twelve days post surgery weighed less, were shorter, but had a normal body composition as determined by the Lee Index, and were hypophagic (grams eaten/day). The animals were placed into individual, self-contained feeding modules and given powdered chow. After familiarization to the modules, meal parameters were recorded continuously by a computer for an eight day period. While dark phase meal frequency did not differ significantly between groups, the lesioned rats took more meals during the light period. Over the eight-day measurement period DMNL rats were hypophagic compared to SCON in absolute terms. However, when total intake and meal size were normalized to metabolic size, these two parameters did not differ significantly between groups. Upon refeeding, after a one-day fast, the initial meal size of the normally hypophagic DMNL rats exceeded that of SCON. Rats with DMNL have previously been shown to have deficits in some hypothesized short-term food intake control mechanism (e.g., cholecystokinin, glucose sensing). Thus overeating by the lesioned rats after a fast could possibly result from a specific short term control deficit.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies

This review article discusses the well-established role of the dorsomedial hypothalamic nucleus (DMN) in feeding, drinking and body weight (BW) regulation. DMN lesions (L) in both weanling and mature rats of both sexes produce hypophagia, hypodipsia and reduced ponderal and linear growth in the presence of normal body composition. The growth reduction is not due to a deficient secretion of growth hormone, insulin-like growth factor-1, thyroxine, triiodothyronine or insulin. DMNL rats actively defend their lower BW (BW settling point) by becoming either hyper- or hypophagic, depending on the experimental manipulation, thereby defending both lean and fat mass. They also regulate their 24-h caloric intake, but they may overeat during the first hour of refeeding following a fast, possibly due to a reduced ability to monitor blood glucose or to respond to cholecystokinin (CCK). 2-Deoxy-D-glucose (2DG) increases c-fos expression in orexin-A neurons in the DMN, and DMNL eliminated the orexigenic effect of 2DG. DMNL rats on high-fat diets do not get as obese as controls, which may be due to a reduction of DMN neuropeptide Y (NPY). Rats lacking DMN CCK-A receptors are obese and have increased expression of NPY in the DMN, supporting earlier data that CCK may act at the DMN to suppress food intake. Excitotoxin studies showed that loss of DMN cell somata, and not fibers of passage, is important in the development of the DMNL syndrome. The DMN is a site where opioids increase food intake and knife-cut studies have shown that fibers traveling to/from the DMN are important in this response. An interaction of glucose and opioids in DMN may also be involved in the control of food intake. DMN knife cuts interrupting fibers in the posterior and ventral directions additively produce the hypophagia and reduced linear and ponderal growth observed after DMNL. Ventral cuts may interrupt important connections with the arcuate nucleus. Lateral and posterior DMN cuts additively produce the hypodipsic effect seen after DMNL, but DMNL rats respond normally to all water-regulatory challenges, i.e., the hypophagia is not due to a primary hypodipsia. The DMN has been shown to be involved in the rat's feeding response to an imbalanced amino acid diet. These data show the DMN has an important role in many processes that control both food intake and BW regulation.     

Consistency of cholecystokinin satiety effect across deprivation levels and motivational states

A gastrointestinal hormone, cholecystokinin (CCK), has recently been implicated in the regulation of meal size. The consistency of the CCK satiety effect was examined across deprivation levels and motivational states. In a series of experiments rats were food deprived for varying amounts of time and injected with various doses of the CCK octapeptide before consuming a test meal of a liquid diet. In Experiment 1, 20 rats were deprived for 5 or 19 hr and injected with 0, 15, and 40 Ivy dog units/kg (U/kg) of CCK and in Experiment 2, 18 rats were 48 hr deprived and were injected with 0, 40, or 80 U/kg of CCK. In Experiment 3, 12 rats were deprived for 92 hr and received 80 U/kg of CCK. In all experiments CCK produced a dose-related suppression in food intake. CCK did not appear to become less effective as deprivation increased: 15 U/kg suppressed intake by approximately 30% at 5 and 19 hr deprivation; 40 U/kg suppressed intake by approximately 50% at all three deprivation levels; 40 U/kg suppressed intake by approximately 72% at 48 hr deprivation and 66% at 92 hr deprivation. In Experiment 4, the effects of CCK on food consumed in absence of hunger (0 hr deprivation) were observed by administering hypertonic saline to food-sated rats before presentation of a liquid diet. Under these conditions 40 U/kg of CCK suppressed intake by 76%. An additional experiment indicated that the increased inhibitory effects observed in the latter experiment were not due to the added variable of thirst. Thus under a wide variety of deprivation conditions and under varying motivational states CCK is remarkably consistent in its inhibitory effects on food intake, which are best described by a constant percent of control intake.     

Increased sensitivity of Zucker obese rats to naloxone is present at weaning

Increased pituitary and plasma concentrations of opioid peptides in genetically obese rodents may be a cause or consequence of obesity. It has been shown that food intake is decreased more in adult genetically obese rats and mice than lean rats and mice by administration of naloxone, an opiate antagonist. Evidence for an opiate-mediated component in the development of rather than the consequence of obesity would be provided if young, not yet obese, genetically obese rats were more sensitive than lean rats to naloxone. In the present experiment two groups of male and female obese and lean Zucker rats, fasted for 2 hr before the onset of the dark portion of the 12-hr light-dark cycle, were administered 0.125 to 0.5 mg/kg naloxone or 0.5 to 2.0 mg/kg naloxone subcutaneously and 30- and 60-min food intakes were measured. In the group administered the lower doses of naloxone, obese rats of the three ages tested responded more than the lean rats after 30 min (70 vs. 79% of control, p less than 0.02). However, increased sensitivity occurred during the 0-60 min period in rats 4-5 weeks old and 0-30 min period in rats 8-9 and 12-13 weeks old. In the second group tested with the higher doses, the obese responded less than the lean rats (73 vs. 66% of control, p less than 0.05) and there was no difference in response after 0-60 min (66 vs. 61% of control, NS). Thus, increased sensitivity to threshold doses of naloxone occurs before the development of substantial obesity and therefore opiate peptides may play a causal role in obesity.     

Plasma hormone levels in growth-retarded rats with dorsomedial hypothalamic lesions

Rats with lesions in the dorsomedial hypothalamic nuclei (DMNL rats) are hypophagic and growth-retarded. Since previous work had shown normal plasma growth hormone and insulin levels in DMNL rats we investigated the diurnal patterns of these and other hormones involved in growth. Trial 1: Rats received electrolytic DMNL or sham operations (SCON). The DMNL rats exhibited no differences from SCON rats in plasma triiodothyronine (T₃), growth hormone (GH), insulin and somatomedin (SM) concentrations, Trial 2: kainic acid, a neurotoxin, was used for lesion production. Again, DMNL rats showed no deficiencies in plasma levels of T₃, GH or insulin. Trial 3: In this experiment, diurnal hormone profiles were assessed. The GH profile and mean 24-hour secretion of both DMNL and SCON groups did not differ significantly. Both groups exhibited a diurnal release of T₃, with the DMNL rats showing slightly higher levels. Plasma insulin rose after dark, i.e., at the onset of feeding, in SCON but not in DMNL rats; the later have a previously reported disrupted feeding rhythm. Glucose patterns were in keeping with insulin profiles. Controls showed a normal plasma corticosterone rhythm whereas DMNL rats had an altered pattern. The data suggest that deficiencies in the principal anabolic and growth-promoting hormones cannot be responsible for the retarded growth of DMNL rats.     

Effect of diet consistency, taste and calories on food intake of weanling rats with dorsomedial hypothalamic lesions

Male weanling Sprague-Dawley rats with dorsomedial hypothalamic lesions (DMNL rats) primarily destroying the dorosomedial hypothalamic nuclei (DMN) showed significant hypophagia on lab chow chunks compared to sham-operated controls. When given a choice between lab chow in the form of chunks or powder, both controls and DMNL rats ate similar amounts of lab chow powder while DMNL rats ate less lab chow chunks. Total caloric consumption was the same as on chunks alone. When returned to lab chow chunks as the only source of calories, the pattern and magnitude of intake was again depressed for the DMNL rats. When offered a choice between Ginger Snaps cookies in chunk form versus powder, DMNL rats remained hypophagic in terms of chunk consumption while the intake from powder was similar in both controls and DMNL rats. When offered a choice between chunks of lab chow and Ginger Snaps, DMNL rats were again hypophagic on lab chow chunks, ate the same as the controls of the cookies, and the total caloric intake was of the same magnitude and pattern as observed in previous tests. The data suggest, but do not conclusively show, that DMNL rats are not hypophagic because they have an aversion to chewing hard food and that, when offered a diet similar in hardness to lab chow chunks i.e., hard cookies, will prefer the less tasty but nutritionally complete lab chow. They are apparently capable of choosing a diet for complete nutrition and, as previously reported, can meter calories competently.     

Long-term effects of insulin in weanling rats with dorsomedial hypothalamic hypophagia: Food intake,efficiency of food utilization,body weight and composition

Twenty-five day-old Sprague-Dawley rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. Two weeks after the operation the DMNL rats showed reduced (p<0.001) body weight and food intake but normal body composition (Lee Index) and efficiency of food utilization (EFU). During the following 32 days subcutaneous administration twice daily of intermediary-acting insulin in increasing doses (mean daily dose 2.64 IU/kg) caused highly significant increases in food intake in both groups. Injection for the subsequent 14 days of higher doses of insulin (mean daily dose 5.64 IU/kg) caused dramatic increase in both food intake and Lee Index and equalized the rate of weight gain with that of the controls. However, in absolute terms the DMNL rats remained consistently hypophagic and weighed significantly less than the controls. Both DMNL rats and controls showed the same EFU during both periods of insulin administration. On discontinuation of hormone treatment during the subsequent 20 days, food intake and body weight gains returned to pretreatment values and the insulin-induced increased Lee Index returned into the low-normal range. However, EFU was significantly (p<0.05) decreased during this period. At sacrifice, plasma glucose, glycerol, free fatty acids and total protein and carcass lipid and protein were normal in the DMNL rats. Absolute and relative (per 100 g body weight and per metabolic size) weight of epididymal fat pads, pituitaries, adrenals and kidneys were normal in the DMNL rats but testes weight per 100 g body weight was higher (p<0.05) in the DMNL rats. Although DMN lesions may remove some glucose-sensitive elements within the hypothalamus, the animals are still capable of responding to the food intake and weight-promoting properties of insulin, as do intact animals.     

Feed efficiency in growth-retarded rats with ventromedial and dorsomedial hypothalamic lesions produced shortly after weaning

Weanling male rats received electrolytic lesions (L) in the ventromedial (VMN) and dorsomedial (DMN) hypothalamic nuclei; sham-operated rats served as controls. The animals were maintained for various periods up to 50 postoperative days on lab chow under standard conditions. In a short-term study, food intake and body weights were measured daily and body weight gain was divided by the food eaten to obtain the efficiency of food utilization. Also, gains in metabolic size ($\text{kg}\text{3}\text{4}$) were divided by food eaten. Both manipulations showed that DMNL rats, except for the first two postoperative days, utilized food normally. The same changes were obtained for weanling VMNL rats, except that they did not show a decline in utilization during the first two postoperative days. Computation of efficiency of food utilization for both VMNL and DMNL rats over postoperative durations ranging from 7 to 50 days showed that among 12 out of 14 experiments DMNL rats utilized food as well as controls. Out of 8 experiments, rats with VMNL utilized food better for weight gained than controls in one and poorer than controls also in one experiment; in reference to metabolic size they utilized food normally. The foregoing data, gathered from 225 DMNL, 64 VMNL and 181 control rats show quite convincingly that food utilization in both types of experimental animals is unimpaired despite profound reductions in ponderal and linear growth and food intake in the DMNL rat and reduced circulating growth hormone levels in the VMNL rat.     

2-deoxy-D-glucose inhibits food intake in rats after ventromedial hypothalamic lesions

Changes in food induced by 2 deoxy-D-glucose (2 DG) have been investigated in newly lesioned rats during the two parts of the diurnal cycle. In a first experiment rats were injected with saline or 2 DG (250, 500, 750 mg/kg) at the beginning of the light or the dark period. In a second experiment rats were injected with saline or 2 DG (250 mg/kg) in the middle of the two periods after 0, 2, 4 or 6 hr of fasting. Results show that 2 DG exerts an inhibitory effect on food intake at night, as it does in intact rats, under ad lib conditions or after a short deprivation time. The stimulating effects of 2 DG on diurnal food intake observed in intact rats is not replicated in VMH rats. On the contrary an inhibition of intake follows a short food deprivation. The data suggest that 2 DG stimulates food intake only under metabolic and feeding conditions characteristic of the diurnal phase in intact rats. Since lipogenesis and hyperphagia are observed 24 hr a day in VMH animals, only inhibition could follow 2 DG.     

Dual 24-hour feeding response to 2DG in rats: daytime increase and nighttime decrease

Thirty-six rats were injected IP with 2DG (0, 250, or 500 mg/kg) at 7-day intervals, once at light onset (7 a.m.) and once at dark onset (7 p.m.), and postinjection food intake was monitored for 24 hours. Five hundred mg/kg 2DG caused food intake to rise above control levels during the first 6 hours of daylight, regardless of whether the injection had occurred that morning or the previous evening, whereas intake during the first 6 hours of darkness was consistently below control levels. In a second study, 24 rats were injected first at 7 a.m. (500 mg/kg 2DG or saline), and 7 days later at 7 p.m. (opposite drug), and food was withheld 12 hours until the light:dark period had changed. For 12 hours after food was returned, 2DG again decreased nighttime food intake (Injection 1) and increased daytime intake (Injection 2). 2DG's dual long-term effects cannot be accounted for either by malaise or by an initial action that later is compensated by its opposite. Rather, 2DG (500 mg/kg) appears to exert two independent, opposite alimentary effects which persist 18-24 hours and which change direction with phase changes in the light:dark cycle.     

Liver denervation does not modify feeding responses to metabolic challenges or hypertonic NaCl induced water consumption

Following liver denervation (LD) food intake (FI) and body weights of the LD rats did not vary significantly from sham operated animals (S). Rats were injected intraperitoneally at 0800 hr (light/dark, 12:12, lights off 1230 hr) with saline (SAL), 2-deoxy-d-glucose (2DG): Experiment (EXP) 1, 250 and 400 mg/kg; EXP 2, 100 and 150 mg/kg and insulin: EXP 1, 6 and 12 IU/kg; EXP 2, 0.75 and 1.5 IU/kg. Both LD and S rats increased their FI similarly over SAL following 2DG and insulin. In EXP 1 rats were also injected with glucagon (G) (540 μg/kg) or SAL at 1330 hr. While this dose of G was later shown to cause hyperglycemia no suppression of FI was noted in either group. Later these rats were injected at 0800 hr with (10 ml/kg) SAL or hypertonic NaCl (0.25 M, 0.5 M and 1.0 M). The two highest doses elevated water intake of both groups comparably. In EXP 2 the ad lib chow fed rats were injected with G (540 and 800 μg/kg) or SAL prior to a one hour presentation of a milk diet at 0800 hr. In both groups, after G, meal size and length were significantly and similarly reduced. The data reveal no deficits in the LD rats' response to metabolic and hypertonic NaCl challenges and question what role, if any, liver glucoreceptors have on feeding behavior and liver osmotic receptors have on hypertonic NaCl induced water consumption.     

Effect of hepatic vagotomy and/or coeliac ganglionectomy on the delayed eating response to insulin and 2DG injection in rats

The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.     

Food intake and neuronal activation after acute 2DG treatment are attenuated during lactation

In the present study, we compared the ability of acute peripheral 2-deoxy--glucose (2DG) treatment to induce food intake and increase immediate early gene expression in lactating versus virgin female rats. In Experiment 1, virgin and lactating rats were treated intraperitoneally with either saline or 2DG (400 mg/kg) and their food intake was compared across the next 6 h. In Experiment 2, lactating and virgin rats were given saline or 2DG, sacrificed 1 h later, and their brains were processed for Fos-like immunocytochemistry (FLI). The average number of cells expressing Fos protein within different brain regions was compared among the different groups. Statistical analyses of the data from Experiment 1 show that 2DG produces an increase in food intake in virgin rats, but not in lactating rats. These data correlate with the results from Experiment 2, where 2DG treatment resulted in an increase in FLI within the caudal ventrolateral medulla (cVLM), the paraventricular nucleus of the hypothalamus (PVN), and the supraoptic nucleus of the hypothalamus (SON) of cycling females. In lactating rats, however, 2DG failed to increase FLI in these regions. Together, these results show that the 2DG-induced food intake response is attenuated during lactation and this attenuation is reflected in the activation of neuronal groups that are thought to participate specifically in the food intake response to glucoprivation. Processes mediating this differential response are discussed in terms of the hormonal and metabolic changes that are characteristic of lactation.     

Food intake and behavioral caloric compensation after protein repletion in the rat

The food intake response of rats to intragastrically infused or orally consumed protein was characterized and compared to the response to similarly administered carbohydrate. In Experiment 1, protein hydrolysate loads administered at the beginning of the dark phase via chronic intragastric cannulae led to rapid (complete within 3–4 hr), dose-related suppressions of food intake in comparison to sham loads or to urea loads controlling for volume, concentration and pH. The suppression remained evident in cumulative intake records through 24 hr and represented a greater than caloric compensation for the amount of metabolizeable energy delivered (1.38 and 1.12 kcal/kcal in Experiments 1a and 1b, respectively). In Experiment 2, protein hydrolysate loaded by gavage suppressed food intake significantly more than isocaloric glucose loads (1.32 vs 0.81 kcal/kcal after 24 hr). Water intake in both experiments was elevated by protein loads, although this occurred after the food intake suppression. Differential satiety responses to protein and carbohydrate repletion were shown in Experiment 3 to extend to orally consumed, naturally occurring macronutrients—casein vs starch and disaccharide diets. These data suggest that satiety in the rat is not solely graded with respect to the energy delivered by the preceding meal but rather that repletion with different macronutrients leads to quantitatively (or perhaps qualitatively) different satieties.     

Suppressive effects of naloxone on food and water intake in vagotomized rats

Rats were (1) sham operated and ad lib fed, (2) given bilateral subdiaphragmatic vagotomies or (3) sham operated and pair fed to the vagotomized group. At the start of the dark period, following a 24 hr fast, the animals were tested for the ability of naloxone (0.5, 1.5, 3.0 and 5.0 mg/kg body weight) to suppress food and water consumption. In comparison to saline control injections the data indicated that naloxone was equally effective in suppressing food intake, over a two hour period, in all groups. Similarly naloxone effectively decreased water consumption of all groups in comparison to their saline trials. When the post naloxone data were calculated as a percentage of saline baseline this suppression was, at times, slightly greater in the vagotomized group than in the other groups. However, this may be an artifact of the low baseline intake of the vagotomized group. The results are discussed with relevance to the recent findings of others concerning this subject.     

Ethanol intake increases galanin mRNA in the hypothalamus and withdrawal decreases it

Alcoholism can be viewed as a motivational disorder that results from alterations in brain systems for ingestive behavior. Therefore, it was hypothesized that alcohol intake might alter the expression of hypothalamic peptides that stimulate feeding. Earlier studies showed that hypothalamic injection of the feeding-stimulatory peptide, galanin (GAL), increases the release of dopamine (DA) in the nucleus accumbens (NAc), as does systemic alcohol, leading to a focus on GAL. Results of this study demonstrate the following: (1). Ethanol, injected daily (0.8 g/kg 10% v/v) for 7 days in male rats, markedly increased the expression of GAL but not of neuropeptide Y (NPY). This occurred in specific hypothalamic nuclei, namely the dorsomedial nucleus (DMN), paraventricular nucleus (PVN) and perifornical lateral hypothalamus (PLH). (2). Rats induced to drink ethanol ad libitum, by gradually increasing the concentration from 1% to 9% v/v without adding sugar or flavoring, exhibited a similar stimulation of GAL mRNA in the PVN and GAL immunoreactivity in the DMN and PVN. (3). Rats given increasing ethanol concentrations, with 12 h access starting 4 h into the dark cycle, had a mean blood alcohol concentration of 18 mg/dl and exhibited a similar increase in GAL expression in the DMN and PVN. (4) Withdrawal from the opioid effects of 9% ethanol, produced by injection of naloxone (3 mg/kg sc), reversed this ethanol effect by significantly reducing GAL expression in the DMN and PLH below baseline levels. These studies suggest a possible role for hypothalamic GAL in alcohol abuse.     

Food deprivation dissociates pancreatic glucagon's effects on satiety and hepatic glucose production at dark onset

We compared the effects of different durations of pretest food deprivation on pancreatic glucagon's (PG) satiating and glycogenolytic actions in order to test the hypothesis that stimulation of hepatic glucose production causes PG's satiety effect. Rats were maintained on a 12:12 LD cycle (lights off: 1015) and deprived of food 45 min or 8, 12, 18, or 24 hr before intraperitoneal injection of 400 micrograms/kg PG. Testing began at 1015, the beginning of the dark phase. Food intake was not inhibited after 45 min of pretest food deprivation (30 min change, 2.5 +/- 4.0%, p greater than 0.05), but was inhibited after 8 or more hr food deprivation. The largest inhibitory effect, 16.2 +/- 3.8%, p less than 0.01, occurred after 8 hr food deprivation. In separate experiments, rats were food deprived 45 min or 8 hr, similarly injected, and killed 10 min after refeeding for blood and liver samples. Hepatic glycogen content at meal onset was higher in rats deprived 45 min than in rats deprived 8 hr (3.2 +/- 0.3 vs. 1.7 +/- 0.3% liver weight, p less than 0.01), and PG injection produced a higher level of hepatic vein blood glucose in the less deprived rats (196 +/- 5 vs. 168 +/- 12 mg/dl, p less than 0.05). Thus, in rats tested at the beginning of the dark phase of the LD cycle after 45 min or 8 hr food deprivation, there is an inverse relation between PG's potencies to inhibit food intake and to stimulate hepatic glucose production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opiate antagonists and agonists and feeding in sheep

Recent evidence indicates that endogenous opiate peptides may be involved in the control of food intake. In previous experiments, injection of β-endorphin has stimulated food intake and peripheral injections of the opiate antagonist, naloxone, decreased food intake in rats. In the present experiments, food and water intakes of sheep were measured in response to peripherally administered opiate antagonists and continuous lateral ventricular administration of opiate agonists. Intravenous injections of both of the opiate antagonists naloxone (0.03, 0.062 and 0.125 mg/kg) and 3–4(hydroxyl-phenyl)-3-4-dimethyl-piperidine propiophenone maleate (0.03, 0.062 and 0.125 mg/kg) decreased food intake for up to 90 min in 4-hr fasted sheep. In water-deprived sheep, naloxone did not affect water intake or body temperature for the first 4 hr but depressed 24 hr water intake. Continuous 90-min injection of 26, 51 and 102 nmoles/min of the opiate agonist D-ala²-met-enkephalinamide (DME) increased food intake of satiated sheep. Intravenous injection of 0.125 mg/kg naloxone blocked the increase in food intake elicited by intraventricular injection of DME. In contrast, intraventricular injection of kyotorphin, a releasor of endogenous enkephalin in the brain, did not affect food intake. Thus, in sheep intracerebroventricular administration of opiate agonists increased food intake; peripheral administration of opiate antagonists decreased food intake and blocked the feeding induced by agonists.     

The effect of naloxone on nocturnal food intake in female and male rats

Previous studies have shown that estradiol and progesterone can alter the response of female rats to naloxone. For example, ovariectomized rats receiving estradiol were found to be less sensitive to the anorexic effect of naloxone than ovariectomized rats receiving oil (vehicle) or progesterone. In the present paper, we evaluated the effect of naloxone on nocturnal food intake in female rats during each stage of the estrous cycle to determine whether changing levels of gonadal hormones in intact female rats would affect their response to naloxone. To evaluate the role testosterone might play in modulating the male rat's feeding response to naloxone we studied the effect of peripherally administered naloxone (0.1, 1.0 and 10 mg/kg) on nocturnal food intake of intact, castrate and castrate + testosterone propionate male rats. During late metestrus, diestrus and proestrus, female rats decreased nocturnal food intake following the administration of naloxone (1.0 and 10 mg/kg) SC (p less than 0.05). During estrus, female rats failed to decrease food intake following any of the doses of naloxone administered. The male rat's response to naloxone does not appear to be altered by the presence or absence of testosterone. Thus, the level of estradiol and progesterone at different stages of the estrous cycle may affect the female rat's response to the satiety effect of naloxone.