Taste reactivity in alcohol-preferring AA and alcohol-avoiding ANA rats.

Alcohol-preferring rats (Alko alcohol or AA) were tested for taste reactivity to water, sucrose, quinine, and a range of alcohol concentrations (5-40%) both before and after a period of continuous alcohol access. The alcohol-avoiding line of rats (Alko nonalcohol or ANA) was also tested for comparison. It was found that AA rats displayed greater ingestive reactivity to alcohol compared to ANA rats both before and after a three-week period of continuous access to 10% alcohol (during which time AA rats drank significantly more alcohol than ANA rats). AA rats also made significantly more ingestive responses to a 0.3 M sucrose solution and a 0.0005 M quinine solution. Differences between AA rats and ANA rats in aversive reactivity appeared only after the alcohol consumption tests; AA rats made significantly fewer aversive responses to the 30% and 40% concentrations after continuous alcohol access. AA rats also made significantly more aversive responses to the quinine solution. The results suggest that line differences between AA rats and ANA rats in the reactivity response to alcohol solutions have been selected in association with the original selection phenotype of alcohol consumption.     

Influence of magnesium deficiency on liver collagen after carbon tetrachloride or ethanol administration to rats

The effects of magnesium deficiency on liver collagen after the administration of a hepatotoxic substance were investigated. Rats, fed a control or magnesium-deficient diet (0.040 g/kg), received six CCl4 or mineral oil injections administered at 2-d intervals starting from the first day of diet treatment. They were killed 3 or 12 d after the last injection. Between postinjection d 3 and 12, no change of magnesium concentration in liver was observed in the deficient rats. Three days after the end of treatment liver calcium in the magnesium-deficient CCl4-treated rats was higher than in any other group. Liver collagen of untreated control rats and untreated magnesium-deficient rats was not significantly different. In control and magnesium-deficient animals receiving CCl4 treatment, the liver collagen levels were significantly higher than in untreated rats. The magnesium-deficient rats receiving CCl4 have higher liver collagen than the controls receiving CCl4. In a second experiment the effect of suboptimum intake of magnesium (0.120 g/kg) combined with the ingestion of ethanol was studied in rats given a solution of ethanol in water for 55 d as their only source of fluid. Mortality occurred in the magnesium-deficient rats receiving ethanol, and body weights of these rats were lower than those of animals in the other three groups. The collagen concentration in liver was higher in magnesium-deficient rats consuming ethanol than in any other group. The synergistic action between magnesium deficiency and ethanol therefore appears to be analogous to that observed with CCl4.     

Effect of pancreatectomy or adrenalectomy on the responses of rats to meal-feeding.

The effects of partial pancreatectomy or adrenalectomy and insulin or corticosterone replacement on the responses of rats to meal-feeding were studied. Partial pancreatectomy lowered glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities and resulted in higher blood glucose levels. Partial pancreatectomy did not affect the ability of the animals to adapt to meal-feeding. Insulin supplementation of the pancreatectomized rats restored G6PD and ME activities to those observed in the intact animals and normalized the blood glucose levels in the ad libitum-fed rats. Adrenalectomy decresed the survival of rats subjected to meal-feeding. Eighty percent of the rats died when meal-fed a high glucose diet. Survival was improved when either a 66.5% starch diet or a 40.5% fat diet was substituted for the 66.5% glucose diet. Adrenalectomized meal-fed animals fed 66.5% glucose had higher G6PD and ME activities and higher liver lipid levels than both the adrenalectomized ad libitum-fed and the sham-operated meal-fed rats. Glucocorticoid supplementation lowered G6PD activity in the adrenalectomized meal-fed rats but had no effect on ME activity or liver lipid. Meal-fed adrenalectomized rats had lower liver and serum cholesterol levels than meal-fed intact rats and ad libitum-fed adrenalectomized rats. These cholesterol levels were increased with glucocorticoid supplementation. It was concluded that adaptation to meal-feeding involves an adrenal response to the periodic absence of dietary energy intake, and that the degree of involvement of this response is determined by the composition of the diet.     

Delta receptor antagonism, ethanol taste reactivity, and ethanol consumption in outbred male rats

Naltrexone, a nonspecific opioid antagonist, produces significant changes in ethanol responsivity in rats by rendering the taste of ethanol aversive as well as producing a decrease in voluntary ethanol consumption. The present study investigated the effect of naltrindole, a specific antagonist of delta opioid receptors, on ethanol taste reactivity and ethanol consumption in outbred rats. In the first experiment, rats received acute treatment of naltrexone, naltrindole, or saline followed by the measurement of ethanol consumption in a short-term access period. The second experiment involved the same treatments and investigated ethanol palatability (using the taste-reactivity test) as well as ethanol consumption. Results indicated that treatment with 3 mg/kg naltrexone significantly affected palatability (rendered ethanol more aversive, Experiment 2) and decreased voluntary ethanol consumption (Experiments 1 and 2). The effects of naltrindole were inconsistent. In Experiment 1, 8 mg/kg naltrindole significantly decreased voluntary ethanol consumption but this was not replicated in Experiment 2. The 8 mg/kg dose produced a significant increase in aversive responding (Experiment 2) but did not affect ingestive responding. Lower doses of naltrindole (2 and 4 mg/kg) were ineffective in altering rats' taste-reactivity response to and consumption of ethanol. While these data suggest that delta receptors are involved in rats' taste-reactivity response to ethanol and rats' ethanol consumption, it is likely that multiple opioid receptors mediate both behavioral responses.     

High ethanol preferring rats fail to show dependence following short- or long-term ethanol exposure

AIMS: The high ethanol preferring (HEP) rat shows high total ethanol consumption, high spontaneous activity and high consumption of novel tastants. Because these animals consume large quantities of ethanol daily, we sought to determine whether they could become alcohol-dependent by repeated exposures of varying lengths and withdrawals of alcohol, both in short- and long-term ethanol exposure. METHODS: Male and female HEP rats were subjected to short (14 days) or long (20 weeks) exposure to 10% ethanol in a two choice (vs. water) test. During the short- and long-term ethanol exposures, the animals were repeatedly deprived of ethanol for 5 days followed by reinstatement of the two-choice test. Moreover, pharmacological interventions (morphine and naltrexone), adulteration of ethanol by quinine and addition of saccharine to water were applied to test the lability of a possible alcohol deprivation effect. RESULTS: In every case, deprivation produced a high initial intake of ethanol that lasted 0.5 h, but thereafter no significant increase in alcohol consumption, compared to predeprivation. Even after several months of continuous drinking of large amounts of ethanol, the animals were sensitive to adulteration of the alcohol solution by quinine, that reduced the intake, and still preferred a saccharine solution when presented as a free choice with the alcohol solution. Pretreatment with morphine increased ethanol consumption in the first 0.5 h following deprivation, whereas naltrexone reduced it. CONCLUSIONS: Taste reinforcement is probably a major component of alcohol drinking by the HEP rats, and that while these rats consume large quantities of ethanol both in the short- and long-term, they do not show a robust alcohol deprivation effect.     

Acute ethanol does not always affect delay discounting in rats selected to prefer or avoid ethanol

Aims: The purpose of this study was to determine whether animals predisposed to prefer alcohol possess an altered acute response to alcohol on a delay discounting task relative to animals predisposed to avoid alcohol. Methods: We used rats selected to prefer or avoid alcohol to assess whether genotype moderates changes in delay discounting induced by acute ethanol exposure. Selectively bred rat lines of Sardinian alcohol-preferring (sP; n?=?8) and non-preferring (sNP; n?=?8) rats, and alko alcohol (AA, n?=?8) and alko non-alcohol (ANA, n?=?8) rats were trained in an adjusting amount task to assess delay discounting. Results: There were no significant effects of line on baseline discounting; however, both lines of alcohol-preferring rats exhibit slowed reaction times. Acute ethanol (0, 0.25, 0.5?g/kg) treatment also had no effect on delay discounting in any of the selectively bred rat lines. Conclusion: Our data indicate that in these lines of animals, alcohol preference or avoidance has no impact on delay discounting following acute ethanol exposure. It is possible that other genetic models or lines may be differentially affected by alcohol and exhibit qualitatively and quantitatively different responses in delay discounting tasks.     

Influence of copper status on the response to acute ethanol exposure in rats.

An acute dose of ethanol was used to investigate the biochemical response of tissues with a compromised antioxidant defense system to a surge of oxygen radical production. The copper (Cu)-deficient rat served as the animal model for this study based on its compromised antioxidant defense system. Rats were fed control (10 micrograms Cu/g) or Cu-deficient (0.2 microgram Cu/g) diet for 14 days. In order to minimize secondary effects associated with chronic Cu deficiency, the chelator triethylenetetramine was added to the Cu-deficient diet to shorten the time required for the induction of Cu deficiency. On day 14, rats were gavaged with ethanol (4.5 g/kg b.wt.) or saline and killed 9 hours postgavage. Rats fed the Cu-deficient diets had lower liver superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities than controls. Ethanol treatment had no effect on liver CuZnSOD or Gpx activity, while MnSOD activity was higher than saline control levels following EtOH treatment. Despite low GPx and SOD activity, Cu-deficient rats did not exhibit higher hepatic thiobarbituric acid reacting substances (TBARS) than controls; in fact, hepatic microsomal TBARS were lower in saline-treated Cu-deficient rats relative to Cu-sufficient rats. Ethanol treatment resulted in higher whole homogenate and mitochondrial TBARS than in saline-gavaged rats. Copper status did not influence hepatic TBARS production in response to an acute EtOH load. These data suggest that compensatory mechanisms contribute to the protection of the liver from excessive free radical production in this model of Cu deficiency.     

Influence of ethanol on lead distribution and biochemical changes in rats exposed to lead

In the present study, an attempt has been made to investigate the effect of ethanol consumption on the distribution of lead in different regions of brain and body organs of male albino rats. Lead when administered intragastrically, for a period of eight weeks resulted in almost uniform accumulation of this metal in all the regions of brain, which increased by almost two fold when ethanol was given along with lead. Lead was also seen to compartmentalise in almost all the tissues of the body to varying extents, with the highest accumulation in the kidney. A progressive and appreciable accumulation of lead was seen in blood with a concomitant increase in ZPP levels in animals during the course of treatment, which increased further when ethanol was administered along with lead. The activity of δ-ALAD and AChE in blood was significantly decreased in lead as well as ethanol treated animals. However, in animals coexposed to lead and ethanol, the inhibition of δ-ALAD was not significantly different, when compared to only lead-treated animals. The results suggested that animals exposed to ethanol and lead simultaneously accumulate higher levels of lead in blood and brain of animals making them more vulnerable to the haematological and neurological toxic effects of lead.     

Prenatal ethanol exposure fails to affect stimulus reactivity in the rat

Three groups of male Long-Evans rats, that were the offspring of dams maintained throughout pregnancy on a liquid diet in which 35% of the calories were derived from ethanol, pair fed an isocaloric liquid diet that had maltose-dextrin substituted for the ethanol, or maintained on lab chow and water were used as subjects. All subjects were nursed by foster mothers maintained on lab chow and water throughout pregnancy and lactation. The groups were not found to differ on open field activity or number of approaches to four stimulus objects in an open field at 26-30 days of age, on spontaneous alternation at 50-55 days of age or on response to a novel alley at 55 days of age. It was concluded that in the rat, prenatal ethanol exposure does not result in demonstrable changes in responsivity to stimuli in rats tested after 26 days of age.     

Manganese deficiency: effects on susceptibility to ethanol toxicity in rats

Previous studies have shown that manganese (Mn) deficiency in rats results in reduced activity of manganese superoxide dismutase (MnSOD) and increased levels of mitochondrial lipid peroxidation. These findings suggested to us that the Mn-deficient rat may be especially susceptible to the toxic effects of ethanol, as the metabolism of this compound results in production of superoxide anion. Offspring from Mn-sufficient and Mn-deficient adult rats were given either 20% (wt/vol) ethanol or distilled-deionized water as their drinking fluid for 14 d. Response to ethanol feeding was different between Mn-sufficient and deficient rats as evidenced by severe reductions in caloric intake and body weight observed in the Mn-deficient rats. Furthermore, after 14 d of ethanol feeding, these rats were extremely lethargic and in poor physical condition. Although Mn-sufficient rats responded similarly to the deficient rats during the first 6 d of ethanol feeding, they increased their caloric intake and body weight during the remainder of the experimental period. MnSOD activity in the ethanol-fed Mn-sufficient and Mn-deficient rats was similar, thus the alcohol-induced toxicity observed in the deficient rats was not due to reduced MnSOD activity. Iron-induced lipid peroxidation may be one of the mechanisms leading to the toxicity observed, as ethanol feeding resulted in liver Fe levels that were 30% higher than those in Mn-deficient rats that were not fed ethanol.     

Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake

To investigate mechanisms in outbred animals that increase the propensity to consume ethanol, it is important to identify and characterize these animals before or at early stages in their exposure to ethanol. In the present study, different measures were examined in adult Sprague-Dawley rats to determine whether they can predict long-term propensity to overconsume ethanol. Before consuming 9% ethanol with a two-bottle choice paradigm, rats were examined with the commonly used behavioral measures of novelty-induced locomotor activity and anxiety, as assessed during 15 min in an open-field activity chamber. Two additional measures, intake of a low 2% ethanol concentration or circulating triglyceride (TG) levels after a meal, were also examined with respect to their ability to predict chronic 9% ethanol consumption. The results revealed significant positive correlations across individual rats between the amount of 9% ethanol ultimately consumed and three of these different measures, with high scores for activity, 2% ethanol intake, and TGs identifying rats that consume 150% more ethanol than rats with low scores. Measurements of hypothalamic peptides that stimulate ethanol intake suggest that they contribute early to the greater ethanol consumption predicted by these high scores. Rats with high 2% ethanol intake or high TGs, two measures found to be closely related, had significantly elevated expression of enkephalin (ENK) and galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) but no change in neuropeptide Y (NPY) in the arcuate nucleus (ARC). This is in contrast to rats with high activity scores, which in addition to elevated PVN ENK expression showed enhanced NPY in the ARC but no change in GAL. Elevated ENK is a common characteristic related to all three predictors of chronic ethanol intake, whereas the other peptides differentiate these predictors, with GAL enhanced with high 2% ethanol intake and TG measures but NPY related to activity.     

Effects of concurrent access to a single concentration or multiple concentrations of ethanol on ethanol intake by periadolescent high-alcohol-drinking rats.

The objectives of the current study were to assess the effects of access to different concentrations of ethanol and sex of the animal on ethanol consumption of high-alcohol-drinking (HAD-1 and HAD-2) rats during adolescence [postnatal days (PNDs) 30 through 60]. At the beginning of adolescence (PND 30), the rats were given concurrent access to either a single concentration [15% volume/volume (vol./vol.)] or multiple concentrations [10%, 20%, and 30% (vol./vol.)] of ethanol and water. Analyses of ethanol consumption data revealed significant (P < .025) main effects of line, ethanol condition, and week, and a significant line by sex by ethanol condition by week interaction. For the first week, both male and female HAD-1 and HAD-2 rats consumed more ethanol under the multiple ethanol concentration condition than under the single ethanol concentration condition. However, across the second through fourth weeks, this pattern was seen primarily in male and female HAD-1 rats and to a lesser degree in female HAD-2 rats. In general, female rats consumed more fluids than consumed by male rats, and male rats displayed a higher preference for ethanol over water ratio than observed for their female counterparts. In addition, in comparison with HAD-2 rats, HAD-1 rats drank more ethanol and displayed a higher preference for ethanol ratio. Overall, the current study results indicate that, compared with access to a single concentration (which is used in most studies), concurrent access to multiple concentrations of ethanol produced significantly higher ethanol intakes in periadolescent HAD rats, supporting the suggestion that this ethanol drinking condition would have a greater impact on neuronal development. In addition, although the replicate lines were selectively bred by using the same criteria and foundation stock, the higher ethanol intakes of the HAD-1 line, compared with intakes for the HAD-2 line, seen in the current study support the suggestion that there are some differences in their genetic make-up, affecting ethanol intake, which are expressed during periadolescence.     

Demonstration of lever pressing for oral ethanol by rats with no prior training or ethanol experience

Male rats of the alcohol-preferring AA line were placed in an operant conditioning chamber with one lever delivering 10% alcohol solution and a second giving water. Free food and water were also continually available in the chamber so the animals should not have been motivated to obtain alcohol for reasons of hunger or thirst. The rats had never had alcohol previously. No shaping was used. The rats simply lived for the next 2 weeks in the operant chamber. All of them eventually learned to work for alcohol. Ethanol responding was significantly higher than pressing for water throughout the second week: on the last day, all rats pressed more than 300 times for alcohol and less than 40 times for water, took in a mean of 5.3 +/- 0.2 g/kg of ethanol, and obtained 72% of their total fluid as earned ethanol solution despite the presence of free water. Their acquisition was, however, much slower than that observed in male AA rats that had previously had prolonged access to drinking alcohol in their home cages. Living continually in the operant chamber is thought probably to have been an important factor in enabling the na?ve rats to learn to work for alcohol.     

Plasma lipoproteins and fecal cholesterol excretion in rats drinking ethanol or beer

Three groups of 16 male rats were fed for 7 weeks restricted amounts of the same purified diet, but were given either a glucose solution (group A), ethanol/glucose (group B) or beer (group C), so that energy supply was the same in all groups. Ethanol provided 9% of energy in group B and C. Whole plasma triacylglycerol (TG) concentration rose during the initial 2 weeks in group B (to 140%) and C (to 120%); during the rest of the 7 week observation period there was in all groups about the same fall in plasma TG concentration. Values for cholesterol and phospholipids were alike in all groups. Plasma VLDL components were not significantly different in group A and B; group C had lower amount VLDL unesterified (UC) and esterified (CE) cholesterol, as well as phospholipids and TG than group B. LDL-UC and UC/CE ratio was lower in group C than in group A. HDL₃-UC and UC/CE was higher in group B than in group A, whereas HDL₃-TG was higher in group C than in group A. HDL₂ components were similar in all groups. Fecal excretion of cholesterol was reduced in both groups given alcohol. — The results suggest that various alcoholic beverages might influence plasma lipoproteins differently.     

Effects of ethanol and ipsapirone on the development of midline raphe glial cells and astrocytes.

Previously, results of studies from our laboratory have shown that the offspring of ethanol-fed female rats have a significant decrease in serotonin (5-HT) neurons and glia that contain S100B, an essential trophic factor for the development of 5-HT neurons. The deficiency of S100B-immunopositive glia was detected during the vulnerable period in 5-HT neuron development and in brain areas proximal to these neurons. The reductions of both 5-HT neurons and S100B-positive glia were prevented by maternal treatment with a 5-HT(1A) agonist (i.e., ipsapirone or buspirone). In the current study, we investigated whether the offspring of ethanol-fed rats had a general decrease in the density of glial cells in the brain areas that contain 5-HT neurons, and we determined whether these changes were prevented by maternal treatment with ipsapirone between gestational days (GDs) 13 and 20. We estimated the density of vimentin-positive glia of the midline raphe glial structure (MRGS) at GD 20 and postnatal day (PND) 5 and of glial fibrillary acidic protein (GFAP)-positive astrocytes proximal to the dorsal and median raphe at PNDs 5 and 19. The results of this study provide evidence that in utero ethanol exposure is associated with a reduced density of GFAP-immunopositive astrocytes proximal to the dorsal and median raphe. Maternal ipsapirone treatment significantly increased astroglial density in the dorsal raphe at PNDs 5 and 19 and in the median raphe at PND 5, such that it either prevented (dorsal raphe, PNDs 5 and 19) or blunted (median raphe, PND 5) the effects of ethanol.     

Minimal exposure to ethanol increases ethanol preference in Maudsley reactive male rats.

Male Maudsley reactive (MR/Har) rats often exhibit marked ethanol or alcohol preference (AP) after forced (one-bottle) exposure to 10% [volume/volume (vol./vol.)] ethanol, but exhibit variable AP without this exposure. In this study, we examined manipulations of one-bottle exposure to ethanol (10% ethanol as the sole source of fluid) in three experiments. In Experiment 1, we recorded voluntary consumption of 10% ethanol during 5 weeks of two-bottle choice in male and female MR/Har rats after 0, 1, 2, 3, or 4 days of one-bottle ethanol exposure. The results showed that, in male rats, one day of one-bottle exposure was as effective as multiple days in increasing AP relative to findings for ethanol-naive (control) rats. Female rats were not affected by one-bottle exposure. They drank equal amounts of ethanol across all groups and in greater amounts than observed for male rats (relative to body weight). The results of Experiment 2 supported the suggestion that 18 h of exposure to ethanol was similar to 24 h of exposure for increasing subsequent ethanol consumption, and that 12 h of exposure increased AP relative to findings for ethanol-naive rats, but on a delayed basis and at a lower level than that observed for 24 h of exposure. In Experiment 3, we tested whether these increases in ethanol consumption, observed in male MR/Har rats after one-bottle exposure to ethanol, might be related to habituating to an unpalatable substance. Thus, rats had one-bottle tests with either a 10% ethanol solution (as in earlier studies) or a 0.01 mmol quinine solution, after which groups of rats were tested for voluntary consumption (two-bottle test) of one of these solutions and water. Results showed that although rats in the quinine-exposed group drank more fluid than that consumed by rats in the ethanol-exposed group during the one-bottle period, rats preferred ethanol to water and avoided quinine relative to water during the 5 weeks of two-bottle choice. The results seem to indicate that relatively small amounts of 10% ethanol can markedly increase subsequent AP in male MR/Har rats, and that this increase in AP does not seem to be attributable to a process of habituating to an unpalatable fluid.     

Influence of dichloromethane on the disappearance rate of ethanol in the blood of rats

Summary 24 Albino-Wistar rats were exposed to dichloromethane-vapours in a concentration of 4200 ppm over a period of 4 hrs after intraperitoneal application of 2.0 g ethanol per kilogram body weight. The disappearance rate of ethanol was measured between the 80th and 240th min after the beginning of the exposure. In comparison to a control group of 24 other rats not exposed to dichloromethane the blood ethanol concentrations turned out to be significantly higher, although an influence of dichloromethane on the ethanol metabolism could not be demonstrated.     

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.     

Energy balance in rats with obesity-producing hypothalamic knife cuts: effects of adrenalectomy

Rats with obesity-producing, hypothalamic knife cuts (KC) were fed a purified high fat diet for 9 wk. KC rats consumed more energy (+70-100%) and retained energy with a much higher efficiency than control rats. Adrenalectomy of KC rats 1 wk (before gross obesity was evident) or 5 wk (when KC rats were 70% overweight) after KC surgery caused a reduction in energy intake to levels approximating those of control rats. Furthermore, energy retention in adrenalectomized KC rats was depressed more than could be explained on the basis of the reduction in energy intake. Two factors associated with the reduction in energy retention, urinary excretion of norepinephrine, an indicator of sympathetic nervous system activity, and GDP binding to brown adipose tissue mitochondria, an indicator of the thermogenic capacity of the tissue, were higher in vadrenalectomized KC rats than in pair-fed KC rats. Removal of the adrenals not only suppressed hyperphagia in KC rats fed a high fat diet, but also increased energy expenditure per kilocalorie consumed.