Effect of sulfosulfuron on the urine and urothelium of male rats.

Sulfosulfuron, developed as a herbicide, caused increased microcrystalluria and the formation of urinary tract calculi when fed to male and female rats in a chronic 2-year study at doses of 5,000 ppm and 20,000 ppm. Hyperplasia was also seen in urinary bladders at 5,000 ppm and 20,000 ppm, almost exclusively in the presence of observable calculi/microcalculi. Urinary bladder tumors were found in 2 females in the 5000 ppm group, both in the presence of calculi. No increased microcrystalluria, calculi, or tumors were found at doses of 500 ppm and lower. In the current study, 5 groups of male Sprague-Dawley rats were fed sulfosulfuron at doses of 50, 500, 5,000, and 20,000 ppm for 10 weeks. Ten animals were co-administered 5,000 ppm sulfosulfuron with 12,300 ppm NH4Cl to determine if inhibition of the formation of calculi would prevent any urothelial effects of treatment with sulfosulfuron. Ten animals in the control group and in the high-dose sulfosulfuron group were fed only basal diet for an additional 10 weeks to determine if the effects of sulfosulfuron on the bladder epithelium were reversible. There was an increased incidence of microcrystalluria observed at 5,000 and 20,000 ppm. There was no increase in microcrystalluria observed in the urine of rats co-administered sulfosulfuron and NH4Cl. Urinary bladder calculi were found in the bladder of 1 animal fed 20,000 ppm. Examination by light microscopy showed diffuse papillary/nodular hyperplasia of the bladder epithelium in this animal. No increased microcrystalluria was observed after withdrawal of the chemical from the diet and the bladder epithelium was normal by light microscopy. The hyperplastic effects associated with the feeding of high doses of sulfosulfuron occur only with the appearance of urinary tract calculi. Based on these results and anatomical differences between rats and humans, it may be concluded that the hyperplastic and carcinogenic effects of sulfosulfuron in rats are high-dose, threshold phenomena that are not likely to occur in humans under environmentally relevant exposures.     

Sensitivity of corticosterone and some metabolic variables to graded levels of low intensity stresses in adult male rats

Adult male rats were subjected to different acute stressors, whose intensity was gradually increased, and their corticosterone, glucose, and serum lipid levels were studied. Serum corticosterone was sensitive to graded levels of stress intensities. Glucose followed the same trend. However, serum lipid responses were not related to the intensity of stress. Our results indicate that these latter variables were not sensitive indices of the emotional arousal elicited by brief stress stimuli.     

Sex-specific effects of corticosterone on hippocampally mediated learning in young rats

Glucocorticoids administered during development can have lasting consequences on learning performance and brain development. Whereas most studies administer glucocorticoids to the young rat during the so-called stress-hyporesponsiveness period (SHRP), we examined the effects of corticosterone pellets implanted at the conclusion of the SHRP on two forms of eye blink conditioning (EBC). Analysis of blood samples indicated that pellets implanted on Day 15 released the bulk of the corticosterone before Day 21. In tests of EBC beginning on Day 28, corticosterone-treated males, but not females, showed impaired performance in the hippocampally mediated "trace" version of the EBC paradigm. There were no effects of corticosterone on the "delay" version of the task. These results are consistent with earlier findings that the hippocampus is particularly sensitive to elevated glucocorticoid levels. Moreover, the findings suggest that glucocorticoids administered after the SHRP may produce subtle effects on learning performance akin to those that have been reported in children.     

Naltrexone effects on male sexual behavior, corticosterone, and testosterone in stressed male rats

Chronic physical or psychological stress disrupts male reproductive function. Studies in our laboratory have shown that stress by immersion in cold water (ICW) and by electrical foot shocks (EFS) has inhibitory effects on male sexual behavior; these effects do not seem to be mediated by an increase in corticosterone, nor by a decrease in testosterone. On the other hand, it is known that endogenous opioids are released in the brain in response to these same stressors; consequently, they could be participating in the impairment of sexual behavior, as well as in the changes in corticosterone and testosterone caused by stress. The aim of this study was to analyze the effects of the opioid antagonist naltrexone (NTX) on male sexual behavior, corticosterone, and testosterone in both stressed sexually experienced and naive male rats. Sexually experienced adult male rats were assigned to one of the following groups (n = 10 each): 1) control group, males without sexual evaluation; 2) control group, rats injected ip with saline, non-stressed; 3) control group, rats injected with NTX (3 mg/kg) non-stressed; 4) rats injected ip with saline, and stressed by EFS; 5) rats injected ip with NTX (1.5 mg/kg) and stressed by EFS; 6) rats injected ip with saline and stressed by ICW; 7) rats injected ip with NTX (1.5 mg/kg) and stressed by ICW; 8) rats injected ip with NTX (3 mg/kg) and stressed by ICW. Naive males were assigned to the same control groups but only stressed by ICW and the NTX dose used was 3 mg/kg. Injections were given 30 min before stress sessions. Stress was applied on 20 consecutive days. Male sexual behavior was assessed 15 min after EFS or 30 min after ICW, on days 1, 4, 8, 12, 15, and 20. Trunk blood was collected at the end of the experiments on day 20 of stress. Corticosterone and testosterone were evaluated by HPLC.Mount, intromission and ejaculation latencies were longer in control saline naive males compared to control saline sexually experienced males on the first day. NTX administration to control naive males caused a decrease in mount, intromission, and ejaculation latencies, as well as an increase in ejaculatory frequency/30 min, compared to control-saline only on day 1. Stressed naive males showed higher mount, intromission and ejaculation latencies, compared to control and stressed sexually experienced males, as well as comparable increase in corticosterone and decrease in testosterone plasma levels. NTX administration before exposure to stress prevented the modifications caused by stress in sexual parameters. Sexual behavior in control sexually-active males injected with saline or NTX was not modified. Saline stressed males showed the previously reported alterations in sexual behavior, as well as an increase in corticosterone and a decrease in testosterone plasma levels. Stressed males injected with NTX before exposure to stress showed no alterations in male sexual behavior. NTX in control non-stressed males did not modify corticosterone plasma levels, but did cause a significant increase in plasma testosterone. The increase in corticosterone and the decrease in testosterone due to stress, were attenuated with the opioid antagonist, both in naive and sexually experienced males. Prevention of ICW stress effects was more effective with higher doses of NTX (3 mg/kg). These data suggest that endogenous opioids could be participating in the effects caused by stress on male sexual behavior, corticosterone, and testosterone.     

Chronic stress and plasma catecholamine and corticosterone levels in male rats

Rats were exposed repeatedly to an immobilization, light and noise stressor for 3 weeks and re-exposed to the same stressor after a rest period of 3 weeks. At the beginning of each stress period, blood was obtained by a tail vein cut. Norepinephrine (NE), epinephrine (E) and corticosterone (COR) were determined. The stress response of NE or E remained relatively constant throughout 3 weeks of chronic stress. The stress response of COR remained constant for the first 2 weeks but increased markedly thereafter. After a 3-week recovery, repeat stress values of E were the same while those of NE and COR were significantly lower as compared with the last chronic stress value. Marked individual differences among rats were observed. Thus, the initial stress response during chronic stress showed no adaptation but actual sensitization for COR.     

The effects of stress on play and home cage behaviors in adolescent male rats

One prominent feature of adolescence is the high frequency of social behaviors, such as play. Engaging in these behaviors appears necessary for proper socio‐emotional development as social isolation during adolescence typically leads to behavioral dysfunctions in adulthood. The present experiments examined the effects of stress on social and nonsocial behaviors in group housed adolescent male rats. We found that acute restraint stress led to a complete inhibition of play (e.g., nape contacts and pins) and reduced social investigations in pre‐ (28 days), mid‐ (35 days), and late‐adolescent (42 and 49 days) animals. A follow‐up study, however, found that restraint‐induced suppression of play and social investigations was transient such that experimental animals engage in these behaviors at levels similar to those of controls 1 hr after termination of the stressor. We also found that exposure to repeated restraint stress throughout adolescence led to a decrease in social investigations, while leaving play largely unaffected. Interestingly, in all of the experiments, nonsocial behaviors (e.g., eating, drinking, grooming) were unaffected by restraint, suggesting these effects of stress are specific to social behaviors. Together, these data indicate that both acute and repeated stress significantly affect social behaviors during adolescence. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 52: 62–70, 2010     

The effects of corticosterone and cortisone on the uptake of polyvinyl pyrrolidone and the transmission of immunoglobulin G by the small intestine in young rats.

1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed.     

Effects of ether stress on prolactin and corticosterone levels in prenatally-stressed male rats as adults

The effect of a potent prenatal stressor on adult levels of prolactin and corticosterone was investigated in male rats. It was found that prenatal stress had no effect on initial levels of either of these two hormones. Ether stress levels of prolactin were significantly lower in prenatally-stressed animals compared to prenatally-nonstressed subjects, whereas corticosterone levels in response to ether stress were only marginally affected in prenatally-stressed animals reared by prepartally-stressed mothers. It is suggested that alterations in endocrine function in the adult animal may result from prenatal stress effects on the development of neural mechanisms that regulate the hormonal response to ether stress.     

Excretion of radioactivity in faeces and urine of rats injected with 3H,14C-lipopolysaccharide

The route of excretion of lipopolysaccharide (LPS) and its possible degradation in vivo was studied in rats using biosynthetically radiolabelled LPS from Salmonella abortus equi, carrying 3H activity exclusively in fatty acids and 14C activity in fatty acids and sugars. Following intravenous injection of the above LPS in AS2 rats with or without anaesthesia, excretion of radioactivity occurred mainly in the faeces and to smaller extent in urine. The rate of excretion was slow, a large part of the radioactivity being still present in the liver after 14 days. In faeces the percent recovery of 3H (18%) was lower than that of 14C (32%) suggesting loss of tritium activity and thereby of fatty acids from the excreted LPS. A similar loss of tritium was also found in the material remaining in the liver and spleen 14 days after LPS administration. In urine the material recovered during 14 days (about 7% of injected) was different from the original LPS, 70% of 14C activity being dialysable and practically all 3H activity being volatile. Similar results were also obtained following administration of the LPS intraperitoneally under anaesthesia. However, when the LPS was administered intraperitoneally without anaesthesia, in the majority of the animals, 90% of 14C and 54% of 3H was excreted in faeces within 3 days, suggesting that both route of administration and use of anaesthesia during injection influence the subsequent rate of excretion of LPS.     

Hypothalamic aromatase activity in young and old male rats

We studied the capability of hypothalamic tissue from young (3-4 months) and old (22-24 months) male rats to aromatize androgens to estrogens. Aromatase activity was measured in homogenates of brain tissue by using a radiometric assay that quantifies the stereospecific production of 3H2O from [1 beta-3H]androstenedione as an index of estrogen formation. Despite the 40% drop in circulating testosterone (T) levels associated with aging in males, we found that hypothalamic aromatase activity was unaffected by age. This finding suggested that chronic exposure to low levels of circulating T can maintain brain aromatase activity in aged male rats. In an experiment designed to examine the acute response of hypothalamic aromatase activity to induction by T, we found a significant positive correlation between circulating T levels and hypothalamic aromatase activity in both age groups. These results demonstrate that T remains an effective regulator of hypothalamic aromatase in old male rats.     

Excretion of radioactivity in faeces and urine of rats injected with 3H,14C-lipopolysaccharide.

The route of excretion of lipopolysaccharide (LPS) and its possible degradation in vivo was studied in rats using biosynthetically radiolabelled LPS from Salmonella abortus equi, carrying 3H activity exclusively in fatty acids and 14C activity in fatty acids and sugars. Following intravenous injection of the above LPS in AS2 rats with or without anaesthesia, excretion of radioactivity occurred mainly in the faeces and to smaller extent in urine. The rate of excretion was slow, a large part of the radioactivity being still present in the liver after 14 days. In faeces the percent recovery of 3H (18%) was lower than that of 14C (32%) suggesting loss of tritium activity and thereby of fatty acids from the excreted LPS. A similar loss of tritium was also found in the material remaining in the liver and spleen 14 days after LPS administration. In urine the material recovered during 14 days (about 7% of injected) was different from the original LPS, 70% of 14C activity being dialysable and practically all 3H activity being volatile. Similar results were also obtained following administration of the LPS intraperitoneally under anaesthesia. However, when the LPS was administered intraperitoneally without anaesthesia, in the majority of the animals, 90% of 14C and 54% of 3H was excreted in faeces within 3 days, suggesting that both route of administration and use of anaesthesia during injection influence the subsequent rate of excretion of LPS.     

ACTH and corticosterone secretion following insulin in intact and in variously hypothalamic deafferentated male rats

Summary Adult male rats, intact (N) or with posterior (PHD), anterior (AHD) or complete (CHD) hypothalamic deafferentations, were injected with either 0.04 or 0.2 u/100 g b.wt. of insulin. Forty-five minutes later they were decapitated and trunk blood was collected for serum glucose, adrenocorticotropic hormone (ACTH) and corticosterone (CS) determinations. The high insulin dose reduced serum glucose by approximately 50% and elicited a marked increase in serum ACTH and CS levels in all groups of animals as compared to the vehicle-treated group. In contrast, the low insulin dose which reduced serum glucose approximately 30% elicited a significant adrenocortical response only in the intact or PHD groups but failed to stimulate this response in animals with CHD or AHD. These results demonstrate that (1) CNS sites, outside the medial basal hypothalamus (MBH), mediate the adrenocortical response during the initial stages of hypoglycemia by a neural pathway impinging upon the CRF neurons from the rostral direction, and (2) the adrenocortical response during the more enhanced hypoglycemia stages is mediated by a systemic mechanism which acts directly on the MBH.Abbreviation u units of insulin