Disseminated thrombosis and bone infarction in female rats following inhalation exposure to 2-butoxyethanol.

Groups of 10 male and 10 female F344/N rats were exposed to 0, 31, 62.5, 125, 250, and 500 ppm of 2-butoxyethanol (BE) by inhalation, 6 hr/day, 5 days/wk, for 13 wk. Four moribund female rats from the 500 ppm group were sacrificed during the first 4 days of exposure, and 1 moribund female from the same group was sacrificed during week 5. Dark irregular mottling and/or loss of the distal tail were noted in sacrificed moribund rats. Similar gross lesions were noted in the terminally sacrificed females exposed to 500 ppm BE. Histologic changes noted in the day 4 sacrificed moribund rats included disseminated thrombosis involving the coccygeal vertebrae, cardiac atrium, lungs, liver, pulp of the incisor teeth, and the submucosa of the anterior section of the nasal cavity. Alterations noted in coccygeal vertebrae from the 500 ppm sacrificed moribund rats included ischemic necrosis and/or degeneration of bone marrow cells, bone-lining cells, osteocytes (within cortical and trabecular bone), and chondrocytes (both articular and growth plate), changes that are consistent with an infarction process. The moribund female rat that was sacrificed during week 5 and those female rats treated with 500 ppm and sacrificed following 13 wk of treatment lacked thrombi, but they had coccygeal vertebral changes consistent with prior infarction and transient or complete bone growth arrest. No bone lesions or thrombi were noted in the male rats treated with the same doses of BE. In conclusion, exposure to 500 ppm BE vapors caused acute disseminated thrombosis and bone infarction in female rats. Possible pathogenic mechanisms are discussed.     

The effect of cholecystokinin octapeptide and glucagon (1-29) on food intake of weanling rats

Cholecystokinin octapeptide (CCK-8) and glucagon (GLG) decrease food intake of a number of species. However, the responsiveness of rats to the food intake effects of these peptides may develop differentially due to sex, age and/or developmental state. Male and female weanling rats decreased early dark cycle food intake following the administration of 5 and 10 micrograms/kg CCK-8 and male rats were more responsive than female rats, p less than 0.05. GLG did not decrease early dark cycle food intake of either male or female weanling rats. Weanling male rats increased plasma glucose and insulin levels in response to GLG administration, p less than 0.05. Male rats were retested with GLG (250 and 500 micrograms/kg) at 6, 9 and 22 weeks of age. GLG did not decrease food intake of these rats until they reached 9 weeks of age and they were still responsive at 22 weeks of age, p less than 0.05.     

Age- and sex-related changes in toluene metabolism by rat hepatic microsomes in vitro

Age- and sex-related changes in toluene metabolism by hepatic microsomes of male and female Sprague-Dawley (SD) rats (1 to 20 weeks) were investigated. A major metabolite of toluene, benzyl alcohol (BA), was measured by high-performance liquid chromatography (HPLC). At low substrate toluene concentrations (0.4 mM), in male rats, BA increased dramatically with development, reaching a peak at 5 weeks of age, rapidly decreasing thereafter. In female rats, BA increased dramatically with development at 3 to 5 weeks of age, and then declined gradually to a low level. Gender differences were obtained at 5 and 20 weeks of age, with BA products being higher in males than in females. At high substrate toluene concentrations (5.0 mM), in male rats, the BA formation pattern was similar to that at the low substrate concentration, although the rate of increase with age was slower. In female rats, a peak was obtained at 3 weeks of age, and then declined gradually to a low level. Gender differences were obtained at 5, 15 and 20 weeks of age, with BA products being higher in males than in females. These results indicate that toluene metabolism exhibits age and gender differences.     

Hyperlipidemia is induced in regucalcin transgenic rats with increasing age

Regucalcin plays an important role as a regulatory protein in intracellular signaling pathway in many cells. Regucalcin transgenic (TG) rats have been shown to induce a remarkable increase in serum triglyceride and HDL-cholesterol concentrations at the age of 36 weeks (35). Furthermore, this was investigated in regucalcin TG rats with increasing age (14, 25, 36 or 50 weeks). Serum triglyceride or HDL-cholesterol concentration was markedly increased in regucalcin TG male and female rats at 14, 25, 36 or 50 weeks of age. Serum-free fatty acid concentration was significantly elevated in regucalcin TG male and female rats at 25, 36 or 50 weeks. In the TG female rats, a significant increase in serum free fatty acid concentration was also observed at 14 weeks of age, while it was not seen in the TG male rats. Serum-free cholesterol concentration was significantly increased in regucalcin TG female rats at 14, 25, 36 or 50 weeks. Such an increase was not induced in the TG male rats. Moreover, serum calcium concentration was significantly raised in regucalcin TG male and female rats at 50 weeks of age. Also, serum albumin concentration was significantly elevated in regucalcin TG female rats at 25, 36, or 50 weeks of age. Such an increase was not observed in the TG male rats. Serum zinc, glucose or urea nitrogen concentration was not significantly altered in TG male and female rats. This study demonstrates that hyperlipidemia is uniquely induced in regucalcin TG rats with increasing age.     

Sex-difference in the age related change of cholesterol metabolism in rats

In Sprague-Dawley rats at the ages of 5 weeks (young) and 9 months (adult), the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in age-matched animals was significantly higher in females than in males. The magnitude of the age-related decrease in the reductase activity was also greater in female rats. When rats were fed a cholesterol-enriched (1%) diet for 30 h as cholesterol challenge, the reduction of reductase activity depended more on sex than on age. The activity of cholesterol 7 alpha-hydroxylase was also higher in female than in male rats and it apparently remained unchanged with age in female rats while it decreased in male rats. With a cholesterol-enriched diet, the hydroxylase exhibited a significant age- and sex-dependent difference and it increased only in young males and adult females. In male rats, the concentration of hepatic cholesterol was significantly higher in adult than in young rats while it was comparable in female rats. The increase in hepatic cholesterol with dietary cholesterol was observed only in male adult rats. A significant age-related difference was observed in the concentration of serum cholesterol. The results suggest an existence of sex-dependent compensatory mechanism for maintenance of hepatic cholesterol homeostasis with age.     

Luteinizing hormone-releasing hormone (LHRH) neurons in the male and female rats at peripubertal period

Summary Luteinizing hormone-releasing hormone (LHRH) neurons were immunohistochemically studied in rats of both sexes at peripubertal ages. The number of immunoreactive LHRH neurons (irLHRH neurons) was counted in the brain region from the level of the septumpreoptic area to the level of the rostral part of the infundibulum in colchicine-treated male and female rats at 30 and 60 days of age. At 30 days, irLHRH neurons were more numerous in male rats than females. At 60 days, the number of irLHRH neurons in female rats increased to the level of male rats of the same age. In non-colchicine-treated rats, the count of irLHRH neuron was quite low. The difference in the number of irLHRH neurons between colchicine-treated and non-treated rats may be regarded as the activity of LHRH system. The difference in the number of irLHRH neurons was larger in male rats than in female rats at 30 days of age. On the contrary, at 60 days of age, the difference was larger in females than in males. LHRH contents were measured in the preoptic-anterior hypothalamic area (POA-AH), where LHRH neuronal perikarya are mainly located, and in the mid-hypothalamic area. LHRH content of the POA-AH in male rats at 60 days of age was not significantly different from that at 30 days of age. While, LHRH content in the POA-AH was greater in 60-day-old female rats at proestrous morning than that in 30-day-old females. At 30 days of age, male rats tended to contain more LHRH in the POA-AH than female rats. However, either at 30 days or at 60 days, no statistically significant differences were detected between male and female rats. In mid-hypothalamic area, LHRH content in 60-day-old male rats was greater than that in 30-day-old male rats. On the other hand, there was no difference in LHRH content between 30-day-old and 60-day-old female rats. At 60 days of age, LHRH content in male rats was greater than that in female rats. The present morphological findings and LHRH measurements suggest that the functional maturation of LHRH system occurred earlier in male rats than in female rats.     

Morphofunctional investigations on spontaneous pituitary tumors in Wistar rats

Adenoma of the pituitary gland represents one of the commonest spontaneous tumors in strains of laboratory rats. In a retrospective survey of pituitary glands from 2165 albino Wistar rats, the total number of pituitary adenomas was 501, representing an overall incidence of 23% with females showing a higher incidence (32%) than males (13%). Pituitary adenoma was rare from 6-52 weeks of age and accounted for only 0.2% of the total incidence. The first pituitary tumors in this series were observed at 32 weeks in 2 female rats and at 40 weeks in a male rat. From 52-85 weeks of age, incidence remained low, and then increased progressively in animals that died from 85-110 weeks of age. In a series of 200 Wistar rats, detailed evaluation was completed for neoplastic and hyperplastic lesions of the pituitary gland. The immunocytochemical characteristics of the pituitary adenoma were investigated using markers for prolactin, growth hormone, and thyrotropic hormone. Positive immunoperoxidase staining revealed an incidence of 59% prolactinomas in both male and female rats. Forty-one percent of pituitary adenomas did not stain for prolactin, thyrotropic, or growth hormone and showed no specific morphologic differences from prolactinomas. The application of immunoperoxidase-staining techniques offers a useful tool for characterizing secretory activity of pituitary adenomas and evaluating histopathologic changes of the pituitary gland.     

Influence of Strain and Sex on the Local Development of Mammary Tumors Induced by Direct Application of DMBA Powder to Rat Mammary Glands

In order to determine the influence of strain and sex on local carcinogenesis in rat mammary tissue, 1 mg of 7, 12 dimethylbenz(a)anthracene (DMBA) was dusted directly onto the exposed mammary gland of 30-day-old Long-Evans (L-E) rats and Sprague-Dawley (S-D) rats. The experiment was terminated 28 weeks after application of the carcinogen. Tumors measuring between 1 and 2 cm in diameter were harvested from female L-E rats with high frequency (85%) and long latency (mean: 23.7 weeks after DMBA dusting), and from female S-D rats with extremely high frequency (98%) and short latency (16.7 weeks). Male rats of both strains were almost identically much less susceptible to DMBA (L-E; 55%, 25.0 weeks, S-D; 53%, 23.9 weeks). Ovariectomized S-D (47%, 24.9 weeks) and orchiectomized S-D (30%, 24.8 weeks) rats, which were gonadectomized at 30 days of age, respectively, were also much less susceptible. A variety of histologies, mostly malignant epithelial, mesenchymal or mixed tumors, were noted in each group. The carcinomatous response in the mammary tissue was much higher in female S-D (96%) than in female L-E (50%) rats, and very low in male and gonadectomized rats (10-20%). In contrast, the sar-comatous response in the mammary tissue was moderate in female and male L-E and male S-D (43-50%) rats, and low in the other groups (15-29%). Acta Pathol Jpn 40: 9–13, 1990.     

Influence of strain and sex on the local development of mammary tumors induced by direct application of DMBA powder to rat mammary glands

In order to determine the influence of strain and sex on local carcinogenesis in rat mammary tissue, 1 mg of 7,12-dimethylbenz(a)anthracene (DMBA) was dusted directly onto the exposed mammary gland of 30-day-old Long-Evans (L-E) rats and Sprague-Dawley (S-D) rats. The experiment was terminated 28 weeks after application of the carcinogen. Tumors measuring between 1 and 2 cm in diameter were harvested from female L-E rats with high frequency (85%) and long latency (mean: 23.7 weeks after DMBA dusting), and from female S-D rats with extremely high frequency (98%) and short latency (16.7 weeks). Male rats of both strains were almost identically much less susceptible to DMBA (L-E; 55%, 25.0 weeks, S-D; 53%, 23.9 weeks). Ovariectomized S-D (47%, 24.9 weeks) and orchiectomized S-D (30%, 24.8 weeks) rats, which were gonadectomized at 30 days of age, respectively, were also much less susceptible. A variety of histologies, mostly malignant epithelial, mesenchymal or mixed tumors, were noted in each group. The carcinomatous response in the mammary tissue was much higher in female S-D (96%) than in female L-E (50%) rats, and very low in male and gonadectomized rats (10-20%). In contrast, the sarcomatous response in the mammary tissue was moderate in female and male L-E and male S-D (43-50%) rats, and low in the other groups (15-29%).     

Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice

Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.     

Sexual motivation is demasculinized, but not feminized, in prenatally stressed male rats

Sexual motivation and copulation in male rats are associated with dopamine release in the nucleus accumbens. Demasculinized copulatory behavior has been demonstrated in prenatally stressed adult male rats. We have previously reported that approximately 80% of prenatally stressed male rats do not exhibit copulation and that no significant changes in nucleus accumbens dopamine release are seen during exposure to estrous females. In the present study, we investigated whether prenatal stress affects sexual motivation in these animals as adults. Pregnant Wistar rats were subjected to immobilization stress for two hours daily from day 15-19 of gestation. The prenatally stressed male offspring at the age of 3 months were allowed contact with receptive female rats for a 30 min period per week for 10 weeks; then, between the age of 5 and 6 months, their sexual motivation and copulatory activity were measured. Sexual motivation was measured in terms of sexual partner preference. The number of visits and the duration of each visit to an estrous female (stimulus female) or to a sexually active male rat (stimulus male) were recorded. Compared with control males, prenatally stressed male rats showed a significantly lower number of visits and a shorter duration of each visit to stimulus females. Prenatally stressed males showed no preference for male or female stimulus rats in terms of the number of visits and the duration of each visit, whereas control rats showed a significantly higher number of visits and duration of visits to female stimulus rats than male stimulus rats. A significant decrease in copulatory activity was observed in the prenatally stressed male offspring compared with control male rats, with most of the prenatally stressed males failing to show copulation. In vivo microdialysis experiments were performed on the nucleus accumbens with concurrent observation of sexual behavior. The prenatally stressed rats that did not exhibit copulation showed no significant changes in nucleus accumbens dopamine release during exposure to a stimulus male behind a wire-mesh barrier and the amount of dopamine release remained at the basal levels during actual physical contact. These results, combined with those of our previous report, indicate that sexual motivation in prenatally stressed male rats is demasculinized, but not feminized.     

A comparison of protein synthesis by liver parenchymal cells isolated from Fischer F344 rats of various ages.

Rates of protein synthesis by intact liver parenchymal cells isolated from male Fischer F344 rats ranging in age from 2.5 to 30 months were determined by measuring the incorporation of [3H] valine into acid-insoluble material and the specific activity of the extracellular valine. The rate of protein synthesis decreased 44% from 2.5 to 18 months and then increased slightly (18%) from 18 to 30 months. There was no dramatic change in the types of proteins synthesized by isolated liver parenchymal cells isolated from 2- or 18-month-old rats as determined by SDS-polyacrylamide gel electrophoresis. The ribosomal-transit time by liver parenchymal cells isolated from 18-month-old rats was 60% higher than the ribosomal-transit time of liver parenchymal cells isolated from 4-month-old rats. The fidelity of protein synthesis by parenchymal cells isolated from 4- and 18-month old rats was compared by measuring the incorporation of p-fluorophenyl alanine (an analogue of phenylalanine) into acid-insoluble material. Although protein synthesis decreased significantly from 4 to 18 months, the fidelity of protein synthesis remained constant.     

Ageing and compositional changes of rat lens

In order to elucidate chemical changes in the lenses of aged animals, carbohydrate and fatty acid compositions were studied in 36 healthy male and female Fischer 344 rats from 3 weeks to 32 months of age. Senile cataract was observed on six lenses of 12 rats aged 28–32 months.The carbohydrate content increased rapidly within 7 months of age and remained constant until 29 months. But the myoinositol content showed a maximum at 7 months of age and aftewards a decreasing trend was observed. In cataractous lenses, the myoinositol content decreased rapidly; sorbitol and fructose showed similar changes although the rates were much lower than that of myoinositol.Lens fatty acids increased steadily during the life span and the ratio of unsaturated to saturated fatty acids was maintained in a narrow range (1.20–1.30). However, the value was significantly altered in cataractous lenses. An age-dependent change was found with nervonic acid, which increased markedly from 1.8% of fatty acids at 3 weeks of age to 6.8% at 29 months. In cataractous lenses, the predominant changes noticed were a rapid decrease of arachidonic acid and a high content of nervonic acid.     

Hepatic vein thrombosis in Buffalo strain female rats ingesting dimethylnitrosamine.

Buffalo strain male and female rats 12 weeks of age ingested 0.0114% dimethylnitrosamine in a semisynthetic diet for 12 weeks. Hepatic vein thrombosis developed along with focal fibrosis of the liver in female rats. Male rats had focal hepatic fibrosis, but not thrombosis of hepatic veins. A high incidence of hepatic vein thrombosis has been observed previously in Buffalo strain rats given carbon tetrachloride and methylcholanthrene simultaneously.     

Effect of enzyme imprinting of liver microsomal monooxygenases upon lifespan of rats.

Effect of the enzyme imprinting by phenobarbital upon alterations of hepatic microsomal monooxygenase activities and lifespan of Wistar rats has been studied. Phenobarbital-sodium (3.5 mg/100 g body weight per day, i.p.) was injected during 1-3 days after birth. This resulted in the enzyme imprinting of the liver microsomal monooxygenases, however, this effect being observed in female but not male rats. In the phenobarbital treated female rats of different age the duration of sleeping time was significantly lower than that in control animals, whereas it did not differ substantially in male rats. The cytochrome P-450 content increased by 34.5% in phenobarbital treated female rats in the age of 12 months in comparison with control animals. A mean lifespan of experimental female rats increased by 17.5% compared to the level of control animals and did not change in male rats. The analysis of survival of animals in Gompertz equation coordinates showed that enzyme imprinting by phenobarbital caused changes in the mortality patterns at different stages of ontogenesis in experimental female but not male rats. An inverse correlation was found between the duration of pentobarbital sleeping time and lifespan of female and male rats.     

Effect of chronic stress on behavior and cerebral oxidative metabolism in rats with high or low positive affect

The 50 kHz ultrasonic vocalizations (USVs) in rats have been associated with positive affect and rewarding experience. We have previously reported that stable inter-individual differences exist in the expression of these USVs (chirps). We have examined the effect of four weeks of chronic variable stress on cerebral oxidative metabolism, and depression and anxiety related behavior in male and female high (HC) and low (LC) chirping rats. Significant differences in regional oxidative metabolic activity as measured by cytochrome c oxidase (COX) histochemistry were found between male and female rats: Females had lower oxidative metabolism in several brainstem areas such as dorsal and median raphe and pontine nucleus, some cortical areas, and reward-related forebrain regions such as striatum and nucleus accumbens, but higher oxidative metabolism in amygdala and related limbic regions. Chronic stress increased oxidative metabolism in several depression-related brain regions in male but not female LC-rats such as amygdala, hippocampus and anterior thalamus. No systematic behavioral effect of stress was evident in females. In LC males, stress elicited increased levels of 22-kHz USVs, earlier and more stable reduction of weight gain, persistently lower sucrose intake and preference, and higher levels of immobility in the forced swimming test. These behavioral changes, accompanied by increased oxidative metabolism in limbic brain regions, indicate greater vulnerability to stress of male LC-rats, and suggest that in males low inherent positive affectivity predisposes to anxiety and affective disorders.     

Differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed normal or low calcium diet

The purpose of this study was to clarify the differential effect of vitamin K and vitamin D supplementation on bone mass in young rats fed a normal or low calcium diet. Ninety female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into nine groups with 10 rats in each group: baseline control, and 0.5% (normal) or 0.1% (low) calcium diet, either alone, or with vitamin K (30 mg/100g, food intake), vitamin D (25 micro g/100 g, food intake), or vitamin K + vitamin D. After 10 weeks of feeding, bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Vitamin K supplementation increased the maturation-related cancellous bone gain and retarded the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation-related cortical bone gain in rats fed a normal calcium diet. Vitamin D supplementation reduced the maturation-related cancellous bone gain, prevented the reduction in periosteal bone gain, and enhanced the enlargement of the marrow cavity, with no significant effect on the reduction in the maturation-related cortical bone gain in rats fed a low calcium diet, and increased the maturation- related cancellous and cortical bone gains with increased periosteal bone gain in rats fed a normal calcium diet. An additive effect of vitamin K and vitamin D on the maturation- related cortical bone gain was found in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on cancellous and cortical bone mass in young rats fed a normal or low calcium diet, as well as the additive effect on cortical bone under calcium sufficient condition.     

Structure of the brain sensomotor cortex in offspring of rats exposed to alcohol

The purpose of the present study was to examine the development of sensomotor brain cortex structures in progeny of male and female rats chronically intoxicated by alcohol. Using the methods of light and electron microscopy and morphometry, the peculiarities of sensomotor cortex cytoarchitectonics, structure on neurons and of their dendrites were studied in rats aged 21 and 30 days, which belong to the progeny of chronically alcoholized male and female animals. Three categories of morphological changes were recognized: the signs indicative of a delay in the neuronal and dendritic maturation, their destructive changes and the repair phenomena, which possess their individual dynamics in postnatal ontogenesis. At 3 weeks of age the extensive destructive changes are seen besides the delay in neuronal maturation and dendritic system underdevelopment. Repair processes increase with age, but the neuronal destructive changes persist, suggesting the delayed mode of action of alcohol intoxication of the animals on the structural brain development in their offspring.     

P-Nitrobenzoic acid alpha2u nephropathy in 13-week studies is not associated with renal carcinogenesis in 2-year feed studies.

The objective of this study was to characterize the renal toxicity and carcinogenicity of p-nitrobenzoic acid in F344 rats. Dose levels in 13-week and 2-year studies ranged from 630-10,000 ppm and 1,250-5,000 ppm, respectively. At 13 weeks, renal lesions included minimal to mild hyaline droplet accumulation in male rats and karyomegaly in male and female rats. At 2 years, renal lesions included proximal tubule epithelial cell hyperplasia in male rats and oncocytic hyperplasia in high-dose male and female rats, and a decreased severity of nephropathy in males and females. The hvaline droplets in renal tubular epithelial cells of male rats at 13 weeks were morphologically similar to those described in alpha2u-globulin nephropathy. Using immunohistochemical methods, alpha2u-globulin accumulation was associated with the hyaline droplets. In addition, at 13 weeks, cell proliferation as detected by PCNA immunohistochemistry was significantly increased in males exposed to 5,000 and 10,000 ppm when compared to controls. Cytotoxicity associated with alpha2U-globulin nephropathy such as single-cell necrosis of the P2 segment epithelium or accumulation of granular casts in the outer medulla did not occur in the 13-week study. In addition, chronic treatment related nephrotoxic lesions attributed to accumulation of alpha2u-globulin such as linear foci of mineralization within the renal papilla, hyperplasia of the renal pelvis urothelium and kidney tumors were not observed. Although there was histologic evidence of alpha2u-globulin accumulation in male rats at 13 weeks, the minimal severity of nephropathy suggests that the degree of cytotoxicity was below the threshold, which would contribute to the development of renal tumors at 2 years.     

Ontogeny of REM rebound in postnatal rats

STUDY OBJECTIVES: The aim of this study was to determine developmental changes (ontogeny) of REM rebound in postnatal rats. DESIGN: Different groups of 2, 3, and 4-week-old experimental rats were instrumentally REM sleep deprived (RSD rats) for 33-48 hours and their sleep was monitored polysomnographically for 48 hours after the REM sleep deprivation (RSD). Age-matched control (RSC) rats also had polysomnographic recordings. SETTINGS: N/A. PARTICIPANTS: Subjects were 18 male Long-Evans RSD rats (5 age 2 weeks, 5 age 3 weeks, and 8 age 4 weeks); and 17 age-matched male Long Evans RSC rats (5 age 2 weeks, 5 age 3 weeks, and 7 age 4 weeks). INTERVENTIONS: Implants for the polysomnographic recordings of the RSD and RSC rats were made by the soft head plug method which permitted continuous, 24 hour/day records during the REM deprivation and post deprivation periods. RSD rats had instrumental RSD by the shaking platform method. RSC rats remained in stationary cages. MEASUREMENTS AND RESULTS: At age 2 weeks, compared with age-matched RSC rats, RSD rats had no REM rebound. At age 3 weeks, compared with age-matched RSC rats, RSD rats had a small but significant REM rebound limited to the first 6 hours after RSD. At age 4 weeks, compared with RSC rats, RSD rats had a larger REM rebound that extended for 18 hours after RSD. The size and duration of REM rebound at the different ages was significantly different. Total sleep lost during the RSD process at each age was made up. CONCLUSIONS: The findings possibly indicate that in rats a REM sleep homeostatic process develops between ages 2 and 4 weeks and that a total sleep homeostatic process is already developed by age 2 weeks.