Effects of glucose supplementation on the pharmacokinetics of intravenous chlorzoxazone in rats with water deprivation for 72 h

It was reported that in rats with water deprivation for 72 h with food (dehydration rat model), the expression of CYP2E1 was 3-fold induced with an increase in mRNA level and glucose supplementation instead of food during 72-h water deprivation (dehydration rat model with glucose supplementation) inhibited the CYP2E1 induction in dehydration rat model. It was also reported that chlorzoxazone (CZX) is metabolized to 6-hydroxychlorzoxazone (OH-CZX) mainly via CYP2E1 in rats. Hence, the effects of glucose supplementation on the pharmacokinetics of CZX and OH-CZX were investigated after intravenous administration of CZX at a dose of 25 mg/kg to control male Sprague-Dawley rats and dehydration rat model and dehydration rat model with glucose supplementation. Based on the above mentioned results of CYP2E1, it could be expected that increased formation of OH-CZX in dehydration rat model could decrease in dehydration rat model with glucose supplementation. This was proven by the following results. In dehydration rat model with glucose supplementation, the AUC of OH-CZX was significantly smaller (1900 versus 1050 microg min/ml), AUC(OH-CZX)/AUC(CZX) ratio was considerably smaller (105 versus 34.3%), C(max) was significantly lower (20.6 versus 8.08 microg/ml), total amount excreted in 24-h urine as unchanged OH-CZX was significantly smaller (62.3 versus 42.7% of intravenous dose of CZX), and in vitro V(max) (2.18 versus 1.20 nmol/min/mg protein) and CL(int) (0.0285 versus 0.0171 ml/min/mg protein) were significantly slower than those in dehydration rat model.     

Effects of pregnancy on spatial cognition in female Hooded Long-Evans rats

Studies examining the roles of estrogens and progestins on spatial cognition have been highly contradictory. To determine if the hormonal environment of pregnancy affects spatial cognition, pregnant (n = 7) and virgin (n = 7) Hooded Long-Evans rats were tested in a Morris water maze throughout the 3 weeks of pregnancy and the second week postpartum. Latency to platform, path length, swim velocity, and time in quadrant were compared over trial-days. To compare water maze performance with changes in hormone levels, serum concentrations of estradiol and progesterone were measured on the first, third, and fifth days of testing during the third week of pregnancy. Subjects learned to find the platform as indicated by decreased time and distance to platform over each trial-week and increased time spent in the quadrant where the platform had been located the previous week. However, there were no differences between treatment groups on time or distance to platform over trial-days. Swim velocity did not differ between or within groups over the 4 weeks of testing. Although primigravid and virgin females were similar in their abilities to learn the novel location of a submerged platform and return to it over time, pregnant animals demonstrated less perseveration to previously learned information and were quicker to locate the platform when it moved to a new location. Thus, reproductive status did not affect reference memory but enhanced working memory in the Morris water maze.     

Effects of mating rate and delayed mating on the fecundity of Adoxophyes orana

Females of Adoxophyes orana F. v. R. (Lepidoptera: Tortricidae) could mate after one day, or after up to 7 days, after eclosion. It was recorded how many eggs per female were laid, had been fertilized and ultimately hatched. Mating rate was assessed by counting the spermatophores in a female.Egg production did not depend on mating rate, but proportion fertilization of eggs from females with three or more spermatophores was reduced. Delayed mating promoted longevity and changed the pattern of oviposition in time. No correlation was found between the proportion hatching of fertilized eggs and any of the other variables in the experiments.The data were introduced into a population model to compute the relation between fecundity and probability to mate.

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Effets du nombre d'accouplements et du retard de la date du premier accouplement sur la fécondité de Adoxophyes orana

Résumé Des femelles de A. orana F. v. R. (Lep., Tortricid.) ont eu la possibilité de s'accoupler le lendemain de leur émergence. Nous avons dénombré l'effectif d'oeufs pondus par chaque femelle, et calculé leur taux de fertilisation et d'éclosion. Les femelles ont été disséquées et les spermatophores comptés pour déterminer le nombre de copulations. La même procédure a été suivie avec d'autres femelles qui ont pu copuler librement jusquà leur mort, (leur longévité a été notée), mais avec une date du premier accouplement pouvant être retardée jusqu'à 6 jours après l'émergence.La production d'oeufs ne dépend pas du nombre de copulations, mais le taux de fertilisation des femelles avec 3 ou 4 spermatophores a été plus faible. Le retard de la date du premier accouplement augmente la longévité, mais réduit légérement le taux de fertilisation. La production d'oeufs était à peu près proportionnelle à la durée de la vie décomptée à partir du moment où la copulation était possible. Aucune corrélation n'a été mise en évidence entre la taux d'éclosion des oeufs fertilisés et les variables de l'habitat.Pour évaluer ces résultats et obtenir plus de connaissances sur les conséquences des copulations retardées, par exemple provenant de procédures d'interruption des copulations, les données ont été introduites successivement dans un modèle de populations pour établir la relations entre fécondité et probabilité d'accouplement.

     

Effects of female and male size on female mating and remating decisions in a bean beetle

The body sizes of individuals of the choosing and chosen sexes in a mate choice may affect sequential mating of females. We examined the effects of the body sizes of females and their mates on attributes of female first mating, and the effects of body sizes of females and their previous and potential future mates on female remating in the adzuki bean beetle, Callosobruchus chinensis. Large- and small-sized adults were derived from larvae reared under conditions of low and high density in a bean, respectively. The speed of first mating of large females was not affected by the size of courting males, whereas small females initiated mating more rapidly when courted by small males. The remating probability of large females was not affected by first male size, whereas small females that mated first with smaller males were more likely to remate. These data suggest that pre- and post-copulatory female choices for male size depend on the female’s size, and the small females might be more willing to copulate with smaller males but prefer larger males to sire their offspring after copulation. A possible explanation for this preference is that small females may suffer greater harm from copulating with larger males.     

Influence of single-sire and multiple-sire natural mating on pregnancy rate of beef heifers

Twelve mature Angus bulls possessing similar semen quality were used to study the effects of single and multiple services and single-sire and multiple-sire mating on pregnancy rate of beef heifers. Heifers were observed for natural estrus twice daily and mated within 6 hr of onset of estrus. Pregnancy rate was determined by rectal palpation at 60 days post-mating. Pregnancy rate of heifers receiving one service per estrus averaged 62.1% (n=124) and pregnancy rate of heifers receiving multiple services (single-sire) per estrus averaged 62.9% (n=105). Pregnancy rate per estrus of heifers mated to three sires (multiple-sire, one service per sire; 74.0%, n=123) was significantly higher than that of heifers mated to a single sire (62.9%). The range in pregnancy rate per bull for single-sire matings was large (0 to 95%), but this range was reduced among the same bulls used for multiple-sire matings (68 to 84%). These results indicate that pregnancy rate to one service did not differ (P>.10) from pregnancy rate to multiple services among single-sire matings, but multiple-sire matings increased (P<.05) pregnancy rate per estrus by 11% over that obtained with single-sire matings.     

Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats

We evaluated the interplay among estrogen, leptin and thyroid function in the regulation of body mass in female rats. Adult female rats were divided into four groups: control (C, sham-operated), ovariectomized (OVX), ovariectomized treated with estradiol benzoate (Eb) 0.7 or 14 μg/100 g bw per day, during 21 days. OVX led to an increase in body mass, food intake and food efficiency (change in body mass as function of the amount of food ingested) which were normalized by the lower Eb dose, and decreased significantly when the higher dose was given. Serum leptin levels were increased more than two-fold in all ovariectomized groups. Serum T4 levels of the Eb treated OVX were significantly lower than in the controls. Serum T3 and TSH were unaffected by OVX or by Eb treatment. Uterine type 2 iodothyronine deiodinase (D2) activity changed in parallel with serum estradiol: decreased after OVX, returned to control levels after the lower E2 treatment, and increased significantly after the high Eb dosage. The hypothalamic D2 activity was reduced around 30% in all castrated groups, treated or not with estrogen, whereas in the brown adipose tissue the enzyme was not changed. Interestingly, although estrogen-treated OVX rats had lower body weight, serum leptin was high, suggesting that estrogen increases leptin secretion. Our results show that estradiol is necessary for the hypothalamic action of leptin, since the increase in leptin levels observed in all ovariectomized rats was associated with a decrease in food intake and food efficiency only in the rats treated with estrogen.     

Testosterone,androstenedione and dihydrotestosterone: Effects on mating behavior of male rats

The relative effectiveness of testosterone, androstenedione, and dihydrotestosterone in maintaining mating behavior following castration of male rats was studied. In Experiment 1 testosterone, but not dihydrotestosterone, was found to maintain mating. In Experiment 2 testosterone and androstenedione were found to be equally effective in maintaining mating. Dihydrotestosterone failed to maintain mating and was no more effective than no treatment at all. Testosterone, androstenedione, and dihydrotestosterone significantly enhanced seminal vesicle and penis weight. In Experiment 3 castrated male rats were administered radiolabeled testosterone, androstenedione, or dihydrotestosterone. Radioactivity was found in hypothalamic and seminal vesicle samples indicating that these steroids can be accumulated by brain as well as peripheral androgen-sensitive tissues. It was concluded that the peripherally active steroid dihydrotestosterone probably plays no role in the maintenance of sexual behavior.     

The effects of pregnancy,lactation, and primiparity on object-in-place memory of female rats

Maternal physiology and behavior change dramatically over the course of pregnancy to nurture the fetus and prepare for motherhood. Further, the experience of motherhood itself continues to influence brain functioning well after birth, shaping behavior to promote the survival of offspring. To meet these goals, cognitive abilities, such as spatial memory and navigation, may be enhanced to facilitate foraging behavior. Existing studies on pregnant and maternal rats demonstrate enhanced cognitive function in specific spatial domains. We adopted a novel object-in-place task to assess the ability of female rats to integrate information about specific objects in specific locations, a critical element of foraging behavior. Using a longitudinal design to study changes in spatial memory across pregnancy and motherhood, an advantage in the object-in-place memory of primiparous female rats compared to nulliparous females emerged during lactation not during pregnancy, and was maintained after weaning at 42 days postpartum. This enhancement was not dependent on the non-mnemonic variables of anxiety or neophobia. Parity did not affect the type of learning strategy used by females to locate a cued escape platform on a dual-solution water maze task. Results indicate that the enhancement of object-in-place memory, a cognitive function that facilitates foraging, emerged after pregnancy during the postpartum period of lactation and persisted for several weeks after weaning of offspring.     

妊娠晚期高雄环境对子代雌鼠性腺发育及生殖功能的影响

目的:通过观察妊娠晚期高雄环境对子代雌鼠性腺发育及生殖功能的影响,从而探讨多囊卵巢综合征(PCOS)的可能致病因素.方法:16只妊娠Wismr大鼠被随机分为A、B两组各8只(A为实验组,B为对照组),A,B两组大鼠均取妊娠第15-20天的相同时间于颈部皮下分别注射等量丙酸睾丸酮和中性茶油,均于孕2l天剖宫产,A组子代雌鼠14只,B组12只;观察子代雌鼠脐带血中睾酮(T)水平、出生体重、阴道开口时间和发情周期、出生100天时体重、乳房发育情况及卵巢、子宫的组织形态学改变.结果:①A组子鼠脐带血中睾酮(T)水平明显增高(P＜0.05);②A组子鼠出生体重较B组明显降低,而出生100天时A组子代雌鼠体重明显高于B组(P＜0.05);无明显发情周期;出生100天时乳房数明显低于B组;阴道开口时间较B组无明显差异③A组子代雌鼠子宫积水扩张明显,卵巢中闭锁卵泡较B组明显增加(P＜0.05).结论:妊娠晚期高雄环境下子代雌鼠表现出类似PCOS的性腺发育及生殖功能异常,推测妊娠晚期母体雄激素过高可能是PCOS的早期致病因素.     

Effects of treatment of male and female rats in infancy with mifepristone on reproductive function in adulthood

Treatment of neonatal male and female rats with mifepristone (1 mg s.c. every 2 days from Day 1 to 15 or Day 4 to 18 of life) interfered with the normal development of their reproductive capacities and of the adrenal glands. The effect on the adrenal glands seemed only temporary. Effects on reproductive functions seemed permanent. Female rats developed abnormalities in structure of the oviduct and ovarian capsule reminiscent of effects reported after perinatal treatment with androgen or oestrogen. During adulthood, anovulatory polyfollicular ovaries developed, reminiscent of rats treated with a small dose of androgen in infancy. Males showed retardation of testicular growth and delay of puberty. During adulthood testes did not grow beyond 65% that of normal rats. Sexual behaviour was deficient in that ejaculations occurred only rarely; when ejaculations did occur, fertility was unimpaired. Males treated with mifepristone in infancy exhibited female sexual behaviour as adults after castration and injections of testosterone and oestradiol. All effects pointed to an insufficient action of testicular hormones in infancy to bring about normal 'masculinization'. Mifepristone therefore appears to show 'teratogenic' actions in rats which affect female reproductive tract development and, in males and females, development of the systems underlying normal reproductive activity and functions in adulthood.     

Effects of pregnancy and female sex steroid hormones on calcitonin gene-related peptide content of mesenteric artery in rats

Calcitonin gene-related peptide (CGRP) levels in plasma and the dorsal root ganglia (DRG) are increased during pregnancy and in ovariectomized rats injected with ovarian hormones. Vasodilatory responses to CGRP are also increased in these animals. In the present study, we hypothesized that pregnancy and ovarian hormones elevate the contents of CGRP in perivascular nerves. We assessed CGRP-dependent mesenteric vascular relaxation induced by electrical field stimulation (EFS) and arterial content of CGRP. Because the mesenteric artery represents resistance vessels, segments of mesenteric arteries collected from female rats at different stages of the estrous cycle, pregnancy, or postpartum and from male rats were used in this study. The EFS-induced relaxation in the presence and absence of CGRP(8-37), an antagonist of CGRP, was used to measure CGRP-dependent relaxation, and radioimmunoassay (RIA) of tissue homogenates was used to assess changes in CGRP content in mesenteric branch arteries. The results show that CGRP-dependent, EFS-induced relaxation response was lower in female rats at diestrus and proestrus than in male rats, and no statistically significant differences were observed between Gestational Day 20 and Postpartum Day 2. The RIA revealed significantly lower mesenteric artery CGRP levels in female rats at proestrus, gestation, and postpartum than in female rats at diestrus or in male rats. We conclude that no correlation exists between CGRP-dependent, EFS-induced relaxation and CGRP content in the mesenteric arteries of these animal groups. Because both CGRP levels in DRG and serum are reported to be elevated, the reduced CGRP content in the vasculature during pregnancy and proestrus implicate enhanced basal release of CGRP at the nerve terminal in these animals.     

雷洛昔酚对大鼠垂体的作用

目的 观察雷洛昔酚是否能诱发出催乳素瘤的动物模型以及对PRL水平的影响,以研究雷洛昔酚对大鼠垂体的作用.方法 雌性Wistar大鼠切除卵巢后,分别在皮下埋植含有雷洛昔酚、雌激素和空白硅胶管,术后8周处死大鼠,检测大鼠体重变化、垂体重量变化、血清催乳素(PRL)水平和垂体组织学变化.结果 雷洛昔酚组与阴性对照组大鼠体重无明显统计学差异,与雌激素组大鼠体重具有统计学差异(P＜0.05);雷洛昔酚组与阴性对照组大鼠垂体重相比无明显差异,与雌激素组大鼠垂体重相比具有统计学差异(P＜0.05);雌激素组大鼠血清PRL水平最高,阴性对照组血清PRL水平最低,雷洛昔酚组介于两者之间,分别与雌激素组、对照组相比较差异均具有统计学意义(P＜0.05);雷洛昔酚组与对照组垂体病理为正常细胞形态,雌激素组垂体病理为PRL瘤表现.结论 雷洛昔酚对大鼠垂体有一定的影响,但不能诱发催乳素瘤.     

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the Sprague-Dawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women.