scholarly journals Inflammation-Susceptible Lewis Rats Show Less Sensitivity Than Resistant Fischer Rats in the Formalin Inflammatory Pain Test and With Repeated Thermal Testing

2006 ◽  
Vol 95 (5) ◽  
pp. 2889-2897 ◽  
Author(s):  
William R. Lariviere ◽  
M. Abdus Sattar ◽  
Ronald Melzack
Keyword(s):  
Maternal Separation ◽  
Differential Susceptibility ◽  
Inbred Strains ◽  
Female Rats ◽  
Male Rats ◽  
Thermal Testing ◽  
Baseline Sensitivity ◽  
Lewis Rats ◽  
Thermal Nociception ◽  
Fischer Rats

Comparisons between Lewis and Fischer inbred strains of rats are used frequently to study the effect of inherent differences in function of the hypothalamic-pituitary-adrenal axis on pain-relevant traits, including differential susceptibility to chronic inflammatory disease and differential responsiveness to analgesic drugs. Increasing use of genetic models including transgenic knockout mice and inbred strains of rodents has raised our awareness of, and the importance of, thorough characterization (or phenotyping) of the strains of rodents being compared. Furthermore, genetic variability in analgesic sensitivity is correlated with, and may be caused by, genetically determined baseline sensitivity. Thus in this study, baseline inflammatory and thermal nociceptive sensitivities were measured in awake male and female Lewis and Fischer rats to examine whether the results could explain relevant strain differences reported in the literature. The effect of maternal separation was also examined and no effect was found on nociceptive sensitivity, corticosterone responses, or the development of adjuvant-induced arthritis, a model of rheumatoid arthritis. Lewis rats and female rats were more sensitive to thermal nociception in the tail withdrawal test (mean of 3 trials) than Fischer rats and male rats, respectively. Unexpectedly, the more inflammation-susceptible Lewis rats were less sensitive in the formalin inflammatory nociception test, and showed a significant decrease in sensitivity with repeated thermal nociceptive testing, whereas Fischer rats did not. These results affect the interpretation of previously observed results. Further study of the underlying mechanisms and the relevance to differential susceptibility to chronic inflammation is warranted.

Serum cholesterol levels of inbred rats

1964 ◽  
Vol 207 (3) ◽  
pp. 631-633 ◽  
Author(s):  
David Kritchevsky ◽  
Shirley A. Tepper
Keyword(s):  
Body Weight ◽  
Serum Cholesterol ◽  
Inbred Strains ◽  
Female Rats ◽  
Male Rats ◽  
Liver Cholesterol ◽  
Cholesterol Levels ◽  
Male And Female Rats ◽  
Males And Females ◽  
The Mean

Changes in serum cholesterol levels with age have been studied in male and female rats of three inbred strains (BN, DA, and Lewis) and one random-bred strain (Wistar). The mean serum cholesterol levels at each age differed among strains. Serum cholesterol levels (mg/100 ml) for male rats at 30, 60, and 90 days were: BN-65, 46, and 47; DA-105, 85, and 101; Lewis-79, 76, and 57; and Wistar-64, 63, and 73. For female rats the values were: BN-56, 45, and 47; DA-86, 74, and 91; Lewis-77, 83, and 67; and Wistar-59, 71, and 83. The variation of serum cholesterol with age was different between strains, but similar for males and females within each strain. There was no correlation between body weight and serum cholesterol. Liver cholesterol levels (mg/100 g) determined at 90 days were, for the males, BN-187, DA-233, Lewis-247, and Wistar-300, and for the females, BN-188, DA-244, Lewis-216, and Wistar-249. No correlation with body weight or serum cholesterol was observed.

Distinct gene-sex interactions regulate adult rat cardiomyocyte width and length independently

2002 ◽  
Vol 12 (1) ◽  
pp. 61-67 ◽  
Author(s):  
I. Boutin-Ganache ◽  
S. Picard ◽  
C. F. Deschepper
Keyword(s):  
Genetic Linkage ◽  
Ventricular Hypertrophy ◽  
Inbred Strains ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rat ◽  
Peptide Precursor ◽  
Wistar Kyoto ◽  
Peptide Product

Wistar-Kyoto (WKY) and WKY-derived hyperactive (WKHA) rats are two genetically-related inbred strains of rats that are both normotensive yet exhibit differences in left ventricular mass (LVM). We had shown previously that cardiomyocytes from male WKHA are wider than that of male WKY, and that there was genetic linkage between LVM and a locus on chromosome 5 (RNO5) in the male progeny of a F2 WKHA/WKY cross. We show here that cardiomyocyte width is linked to the same RNO5 locus in male reciprocal congenic rats derived from WKHA and WKY. Contrary to males, we found no genetic linkage between LVM and the RNO5 locus in female rats. However, ventricular hypertrophy in females might be of a different nature, because cardiomyocytes from female WKHA were shorter than their WKY counterparts (with no difference in width). The RNO5 locus contains that of the natriuretic peptide precursor A (Nppa) gene. In male congenic rats, changes in cardiomyocyte width always correlated with reciprocal changes in the LV concentration of atrial natriuretic factor (ANF, i.e., the peptide product of Nppa). Taken together with other functional data, the small size of the RNO5 locus (∼63 cR) increased the likelihood that both cardiomyocyte width and LV ANF concentration could be linked to only one gene (possibly Nppa) in male rats. Moreover, our results support the notion that genes and sex interact to regulate cardiomyocyte width and length independently from one another.

scholarly journals Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Dayan Knox ◽  
Stephanie A. Stout-Oswald ◽  
Melissa Tan ◽  
Sophie A. George ◽  
Israel Liberzon
Keyword(s):  
Risk Factors ◽  
Sex Differences ◽  
Animal Models ◽  
Traumatic Stress ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Male Rats

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.

scholarly journals Microglial synaptic pruning on axon initial segment of dentate granule cells: sexually dimorphic effects on fear response of adult rats subjected to early life stress

2020 ◽  
Author(s):  
Mario A. Zetter ◽  
Angélica Roque ◽  
Vito S. Hernández ◽  
Oscar R. Hernández-Pérez ◽  
María J. Gómora ◽  
...  
Keyword(s):  
Initial Segment ◽  
Maternal Separation ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Freezing Behavior ◽  
Axon Initial Segment ◽  
Female Rats ◽  
Male Rats ◽  
Dentate Granule Cells ◽  
Synaptic Pruning

AbstractAxon initial segments (AIS) of dentate granule cells (GC) in hippocampus exhibit prominent spines during early development that are associated with microglial contacts. Here, we asked if developmental changes in axon initial segment spines (AISS) could be modified by neonatal maternal separation through stress hormones and microglial activation and examined the potential behavioral consequences. We examined AISS densities at postnatal day (PND) 15 and 50, using Golgi-Cox staining and anatomical analysis. Neuron-microglial interaction was assessed using antibodies against ankyrinG, PSD95 and Iba1, for AIS, AISS and microglia, respectively, in normally reared and neonatal maternally separated (MS) male and female rats. We observed a higher density of AISS in MS groups at both PND15 and PND50 compared to control. Effects were more pronounced in female than in male rats. AIS-associated microglia showed a hyper-ramified morphology and less co-localization with PSD95 in MS compared to normally reared animals at PND 15. An MS-like alteration in microglial morphology and synaptic pruning could be produced ex vivo by vasopressin application in acute hippocampal slices from normally reared animals. MS rats exhibited increased freezing behavior during auditory fear memory testing which, like effects on AISS density, was more pronounced in females than males. Freezing behavior was associated with Fos expression in dorsal and ventral dentate GC. In summary, AIS associated microglial activity is altered by MS. Sex differences in the long-term effects of MS on AISS density are penetrant to a behavioral phenotype of increased stimulus reactivity in adult female subjects.

scholarly journals Sex-Linked Differences in the Course of Thioacetamide-Induced Acute Liver Failure in Lewis Rats

2020 ◽  
pp. 835-845
Author(s):  
E KOBLIHOVÁ ◽  
Iveta MRÁZOVÁ ◽  
Z VAŇOURKOVÁ ◽  
H MAXOVÁ ◽  
M RYSKA ◽  
...  
Keyword(s):  
Survival Rate ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Female Rats ◽  
Male Rats ◽  
Preclinical Studies ◽  
Preclinical Research ◽  
Lewis Rats ◽  
General Terms

Acute liver failure (ALF) is a clinical syndrome with high mortality rate, resulting from widespread hepatocyte damage. Its pathophysiological background is still poorly understood and preclinical studies evaluating pathophysiology and new potential therapeutic measures are needed. The model of ALF induced by administration of thioacetamide (TAA) in Lewis rats is recommended as optimal; however, the limitation of previous studies was that they were performed predominantly in male rats. In view of the growing recognition that sex as a biological variable should be taken into consideration in preclinical research, we examined its role in the development of TAA-induced ALF in Lewis rats. We found that, first, intact male Lewis rats showed lower survival rate than their female counterparts, due to augmented liver injury documented by higher plasma ammonia, and bilirubin levels and alanine aminotransferase activity. Second, in female rats castration did not alter the course of TAA-induced ALF whereas in the male gonadectomy improved the survival rate and attenuated liver injury, reducing it to levels observed in their female counterparts. In conclusion, we found that Lewis rats show a remarkable sexual dimorphism with respect to TAA-induced ALF, and male rats display dramatically poorer prognosis as compared with the females. We showed that testosterone is responsible for the deterioration of the course of TAA-induced ALF in male rats. In most general terms, our findings indicate that in the preclinical studies of the pathophysiology and treatment of ALF (at least of the TAA-induced form) the sex-linked differences should be seriously considered.

Influence of housing conditions from weaning to adulthood on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult female rats

2012 ◽  
Vol 112 (9) ◽  
pp. 1474-1481 ◽  
Author(s):  
Sébastien Fournier ◽  
Richard Kinkead ◽  
Vincent Joseph
Keyword(s):  
Maternal Separation ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Housing Conditions ◽  
Juvenile Period ◽  
Hypoxic Conditions ◽  
Fraction Of Inspired Oxygen ◽  
The Impact

Housing conditions affect animal physiology. We previously showed that the hypoxic ventilatory and thermoregulatory responses to hypoxia of adult male rats housed in triads during the juvenile period (postnatal day 21 to adulthood) were significantly reduced compared with animals housed in pairs. Because sex hormones influence development and responsiveness to environmental stressors, this study investigated the impact of housing on the respiratory and thermoregulatory physiology of female rats. Since neonatal stress attenuates the hypoxic ventilatory response (HVR) of female rats at adulthood, experiments were performed both on “control” (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3–12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions [fraction of inspired oxygen (FiO2) = 0.12; 20 min]. The ventilatory and body temperature responses to hypoxia of female rats raised in triads were reduced compared with rats housed in pairs. Housing female rats in triads did not affect basal or hypoxic plasma corticosterone levels but did increase levels of estradiol significantly. We conclude that modest changes in housing conditions (pairs vs. triads) from weaning to adulthood does influence basic homeostatic functions such as temperature and respiratory regulation. Triad housing can reverse the manifestations of respiratory instability at adulthood induced by stressful neonatal treatments. This should raise awareness of the benefits of increasing social interactions in clinical settings but also caution researchers of the potential impact of such subtle changes on experimental protocols and interpretation of results.

Effects of maternal separation on the dietary preference and behavioral satiety sequence in rats

2014 ◽  
Vol 5 (3) ◽  
pp. 219-228 ◽  
Author(s):  
M. C. da Silva ◽  
J. A. de Souza ◽  
L. O. dos Santos ◽  
I. L. Pinheiro ◽  
T. K. F. Borba ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Maternal Separation ◽  
Light Exposure ◽  
Caloric Intake ◽  
Female Rats ◽  
Male Rats ◽  
Serum Triglycerides ◽  
Dietary Preference ◽  
Satiety Sequence ◽  
Behavior Of Rats

This study investigated the effects of maternal separation on the feeding behavior of rats. A maternal separation model was used on postnatal day 1 (PND1), forming the following groups: in the maternal separation (MS) group, pups were separated from their mothers each day from PND1 to PND14, whereas in the control (C) group pups were kept with their mothers. Subgroups were formed to study the effects of light and darkness: control with dark and light exposure, female and male (CF and CM), and maternal separation with dark and light exposure, female and male (SDF, SDM, SLF and SLM). Female rats had higher caloric intake relative to body weight compared with male controls in the dark period only (CF=23.3±0.5 v. CM=18.2±0.7, P<0.001). Macronutrient feeding preferences were observed, with male rats exhibiting higher caloric intake from a protein diet as compared with female rats (CF=4.1±0.7, n=8 v. CM=7.0±0.5, n=8, P<0.05) and satiety development was not interrupted. Female rats had a higher adrenal weight as compared with male rats independently of experimental groups and exhibited a higher concentration of serum triglycerides (n=8, P<0.001). The study indicates possible phenotypic adjustments in the structure of feeding behavior promoted by maternal separation, especially in the dark cycle. The dissociation between the mother’s presence and milk intake probably induces adjustments in feeding behavior during adulthood.

scholarly journals The long-term effects of repeated heroin vapor inhalation during adolescence on measures of nociception and anxiety-like behavior in adult Wistar rats

2021 ◽  
Author(s):  
Arnold Gutierrez ◽  
Eric L. Harvey ◽  
Kevin M. Creehan ◽  
Michael A. Taffe
Keyword(s):  
Drug Use ◽  
Elevated Plus Maze ◽  
The United States ◽  
Female Rats ◽  
Male Rats ◽  
Long Term Effects ◽  
Health Crisis ◽  
Thermal Nociception ◽  
Plus Maze

ABSTRACTThe United States continues to experience a public health crisis related to the nonmedical use of opioid drugs. Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those caused by drug use initiated during adulthood. The present study examined the effects of repeated heroin inhalation, a common route of administering opioids, during adolescence, on measures of nociception and anxiety-like behavior in adulthood. Rats were exposed twice daily to 30-minutes of heroin vapor from post-natal day (PND) 36 to PND 45. At 12 weeks of age, baseline thermal nociception was assessed across a range of temperatures with a warm-water tail-withdrawal assay. Anxiety-like behavior was assessed in an elevated plus-maze (EPM) and activity was measured in an open field arena. Starting at 23 weeks of age, baseline thermal nociception was re-assessed, nociception was determined after acute heroin or naloxone injection, and anxiety-like behavior was redetermined in the EPM. Adolescent heroin inhalation altered baseline thermal nociception in female rats at 12 weeks of age and in both female and male rats at ∼23 weeks. Heroin-treated animals exhibited an increase in anxiety-like behavior when tested in the elevated plus-maze, showed blunted heroin-induced analgesia, but exhibited no effect on naloxone-induced hyperalgesia. The present study demonstrates for the first time that heroin vapor inhalation during adolescence produces behavioral and physiological consequences in rats that persist well into adulthood.

scholarly journals A severe form of maternal separation in rat consisting of nineteen-day 6-hour daily separation at unpredictable times minimally affects behavior across lifespan and possibly confers protection against some maladaptive outcomes

2021 ◽  
Author(s):  
Tatyana Budylin Behring ◽  
Margaret H Kyle ◽  
Maha Hussain ◽  
Jack Zhang ◽  
Alessia Manganaro ◽  
...  
Keyword(s):  
Life Stress ◽  
Maternal Separation ◽  
Forced Swim Test ◽  
Coping Behavior ◽  
Early Life Stress ◽  
Severe Form ◽  
Female Rats ◽  
Male Rats ◽  
Protective Effects ◽  
Multiple Species

Maternal separation (MS), a type of early life stress, has been associated with adverse socioemotional and behavioral outcomes throughout the lifespan across multiple species. Comprehensive longitudinal biobehavioral characterization of MS in rats is sparse and conflicting, warranting more studies. We conducted an MS paradigm involving 6-hour daily separation at unpredictable start times from P2 to P21. We hypothesized this severe form of MS would lead to developmentally emerging maladaptive biobehavioral consequences from juvenile through adult periods compared to Controls (C), especially in social behaviors. We tested: (1) own dam odor preference shortly after weaning; (2) juvenile and adult anxiety-like, sociability, and play behaviors using the light-dark test, three-chambered social interaction test, and video-coded juvenile play behavior; and (3) adult coping behaviors and neuroendocrine response using the forced swim test and blood corticosterone responses. Our results were mostly diametrically opposed to our initial hypothesis and show MS can, under certain circumstances, be protective against maladaptive biobehavioral outcomes. Recently weaned MS male rats had a stronger preference for their dam's odor. Juvenile MS females spent more time in rough-and-tumble play than C female rats. No differences in sociability were found in the juvenile or adult periods. MS promoted a decrease in anxiety-like behavior that persisted from juvenile to adult periods. Finally, MS led to deficits in coping behavior in male adults, but basal and reactive corticosterone levels were unaltered by MS. More studies are needed to validate our surprising findings and probe the neural mechanisms underlying these protective effects.

INDUCTION OF GOITRE BY PTU OR KClO4 IN MALE AND FEMALE RATS. EFFECT OF GONADECTOMY

1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia
Keyword(s):  
Iodine Content ◽  
High Plasma ◽  
Disc Electrophoresis ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Glucose Levels ◽  
Male And Female Rats ◽  
Tsh Levels

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.

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