Rat Oestrous Cycle Research Articles

Changes of gastric aromatase and portal venous 17β-estradiol during the postnatal development and estrus cycle in female rats

Gastric parietal cells synthesize and secrete a large amount of 17β-estradiol into the portal vein. However, there are few studies on the gastric 17β-estradiol during the postnatal development and estrus cycle. The purpose of this study is to clarify the onset and the prepubertal change of gastric 17β-estradiol synthesis; and the effect of gastric 17β-estradiol on the estrus cycle. Wistar female rats aged from 15 to 40 days and 10 weeks were used in the study. The expression of aromatase and estrogen receptor (ER) α mRNAs and proteins was analyzed in the stomach, ovary, and liver by RT-PCR, immunohistochemistry, and Western blotting methods; and 17β-estradiol levels in the artery and portal vein were assayed by the ELISA method. During postnatal development, aromatase protein and aromatase cells in gastric mucosa and portal venous 17β-estradiol levels started increasing after 20 days, and then these subjects reached nearly the same levels as mature female rats at 40 days. In the estrus cycle, the arterial 17β-estradiol level in proestrus was the highest, and the value was 60 % of the portal venous level. Gastric aromatase protein and portal venous 17β-estradiol levels did not change during the estrus cycle. Ovarian ERα levels fluctuated in the same pattern of arterial 17β-estradiol; however, hepatic ERα levels went unchanged. These results showed that gastric aromatase in females expresses earlier than the sexual maturation, and the gastric aromatase protein reaches the same levels as mature rats at 40 days. Furthermore, 17β-estradiol synthesis and secretion in the stomach is not related to those in the ovary.

ANTI IMPLANTATION AND PREGNANCY INTERRUPTION ACTIVITY OF JAPAKUSUMA (HIBISCUS ROSA SINENSIS) IN ALBINO RATS

Increase in population has affected many socio - economic conditions of people by increasing crimes, illiteracy, destructive activities, diseases, improper food and shelter. Thus to control this population and limit the family size at a personal level and at a national level, modern contraceptive methods and medicines were introduced long back. There are many new contraceptives available now, but they have various side effects. Som e traditional practi ti oners used to dispense oral contraceptives me ntioned in Ayurvedic classics. Such as 1) Pippali ( P iper longum ), Vidanga ( Emblica ribes ) and Tankana ( Sodii Biboras ). 2) Talisapatra ( Taxus baccata ) and Gairika ( Hematite ) with cold water and 3) Kanji bhavita Japakusuma ( Hibiscus rosa sinensis ) . An experi mental study on above mentioned 1 and 2 formulations has proved its efficacy as temporary contraceptive medicine. To evaluate the permanent or long term temporary contraceptive effect of Japakusuma, an attempt was made in this st udy. Study was conducted by Choudary and Khanna method on 18 female, 36 male (for mating) albino rats. Japakusuma, Propylene glycol, Ovral L formed the materials. Single dose was administered on proestrous stage of rat oestrous cycle and observed for anti - implantation and pregnancy interruption activity. Test drug showed significant anti implantation and pregnancy interruption activity. Thus showing the temporary contraceptive activity of Japakusuma ( Hibiscus rosa sinensis ).

Renin antibody staining of reproductive tissues of the rat estrus cycle

Renin is an important kidney vasculature‐produced hormone that is released with a drop in the vascular flow rate through the glomerulus. It activates angiotensinogen, which is altered to angiotensin I, and altered again in lung tissue to angiotensin II, causing a release of aldosterone from the adrenal cortex and an increase in blood pressure, thereby increasing the vascular flow rate through the glomerulus. Renin is also a hox gene product in the mouse, in the abdominal region, found in fetal paired vessels of the abdominal aorta, supplying adrenal glands, kidneys, and gonads. After birth renin is still present in mouse ovarian/uterine artery, but not in the testicular artery. It is also present in giant trophoblast cells of the mouse placenta. Our lab has shown that renin is produced in rat female reproductive tissues, in the ovarian/uterine arteries and giant trophoblast cells, using anti‐mouse renin antibodies. This study examines the sites of renin immunohistochemical staining in rat female reproductive tissues during each stage of the estrus cycle. Anti‐mouse renin antibody generously donated by Dr. Kenneth Gross of RPCI. Research supported by DYC faculty research committee funding.

Effects of Ficus asperifolia on normal rat estrus cyclicity

ObjectiveTo evaluate Ficus asperifolia (Moraceae) (F. asperifolia) effecting on regular estrus cycle of Wistar rats. MethodsAir-dried fruits of F. asperifolia were extracted using water. Prior to the test, vaginal smear was monitored daily for a 3-week period to select females with normal (regular) estrous cycle. Those with regular estrus cycle weighing between 150-170 g were randomized into three sets of 15 animals each. Each set was then divided into three groups: Group 1 (control) was orally administered with distilled water (10 mL/kg body weight) once a day for 1 week starting from the proestrus stage. Groups 2 and 3 were respectively treated with 100 and 500 mg/kg body weight of the plant aqueous extract. The two other sets of 15 animals each were similarly treated as the first set for 3 weeks and 6 weeks respectively. Estrus cycle pattern was monitored before and during plant extract application whereas lipid profile, ovary, uterus and liver growth indices were determined at the end of each treatment. ResultsF. asperifolia did not disrupt (0%) the order of appearance of normal estrus cycle stages, namely, proestrus, estrus, metestrus and diestrus. Short-term treatment (1 week duration) exhibited high frequency of appearance of proestrus and estrus stages while mid-(3 weeks) and long-term (6 weeks) treatments revealed constancy in the frequency of all stages irrespective to animal groups. The plasma and organ lipid profile, as well as ovary, uterus and liver growth remained unchanged when compared to distilled water-treated animals. Following long-term administration of plant extract (6 weeks), no adverse effect was noticed. ConclusionsOur data partially support the use of F. asperifolia in common medicine.

Bupivacaine kinetic changes during the oestrous cycle in rats.

Abstract After a single 20 mg kg−1 i.p. dose during pro-oestrus, oestrus or dioestrus, bupivacaine kinetics in rats were not significantly different except for Cmax which was significantly higher during dioestrus.

Should Atrazine and Related Chlorotriazines Be Considered Carcinogenic for Human Health Risk Assessment?

Chloro-s-triazines have been a mainstay of preemergent pesticides for a number of decades and have generally been regarded as having low human toxicity. Atrazine, the major pesticide in this class, has been extensively studied. In a number of experimental studies, exposure to high doses of atrazine resulted in increased weight loss not attributable to decreased food intake. Chronic studies of atrazine and simazine and their common metabolites show an elevated incidence of mammary tumors only in female Sprague Dawley (SD) rats. On the basis of the clear tumor increase in female SD rats, atrazine was proposed to be classified as a likely human carcinogen by US Environmental Protection Agency (EPA) in 1999. With Fischer rats, all strains of mice, and dogs, there was no evidence of increased incidence of atrazine-associated tumors of any type. Evidence related to the pivotal role of hormonal control of the estrus cycle in SD rats appears to indicate that the mechanism for mammary tumor induction is specific to this strain of rats and thus is not relevant to humans. In humans the menstrual cycle is controlled by estrogen released by the ovary rather than depending on the LH surge, as estrus is in SD rats. However, the relevance of the tumors to humans continues to be debated based on endocrine effects of triazines. No strong evidence exists for atrazine mutagenicity, while there is evidence of clastogenicity at elevated concentrations. Atrazine does not appear to interact strongly with estrogen receptors α or β but may interact with putative estrogen receptor GPR30 (G-protein-coupled receptor). A large number of epidemiologic studies conducted on manufacturing workers, pesticide applicators, and farming families do not indicate that triazines are carcinogenic in these populations. A rat-specific hormonal mechanism for mammary tumors has now been accepted by US EPA, International Agency for Research on Cancer, and the European Union. Chlorotriazines do influence endocrine responses, but their potential impact on humans appears to be primarily on reproduction and development and is not related to carcinogenesis.

Estradiol and Progesterone Regulate the Migration of Mast Cells from the Periphery to the Uterus and Induce Their Maturation and Degranulation

BackgroundMast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus. Moreover, MC degranulation correlates with angiogenesis during pregnancy. The number of MCs in the uterus has been shown to fluctuate during menstrual cycle in human and estrus cycle in rat and mouse indicating a hormonal influence on their recruitment from the periphery to the uterus. However, the mechanisms behind MC migration to the uterus are still unknown.Methodology/Principal FindingsWe first utilized migration assays to show that MCs are able to migrate to the uterus and to the fetal-maternal interface upon up-regulation of the expression of chemokine receptors by hormonal changes. By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation.Conclusion/SignificanceWe propose that estradiol and progesterone modulate the migration of MCs from the periphery to the uterus and their degranulation, which may prepare the uterus for implantation.

178 DISTINCT EXPRESSION AND REGULATION OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTRASE 2 AND ITS POTENTIAL ROLE(S) IN THE UTERUS OF RATS DURING ESTROUS CYCLE

Ectonucleotide pyrophosphatase/phosphodiestrase 2 (ENPP2) is a recently discovered phospholipase D that transforms lysophosphatidylycholine into lysophospatidic acid. Previously, multiple analyses have been carried out to identify oestrogen response genes, such as ENPP2, in the hypothalamus. However, little is known about the role(s) of the ENPP2 gene in the uterus during the oestrous cycle and the mechanism(s) of its regulation. In this study, the ENPP2 gene was investigated using RT-PCR, Western blot, and immunohistochemistry analyses in the uterine of rats. Quantitative PCR analysis demonstrated that the levels of uterine ENPP2 mRNA decreased at oestrus compared with those at proestrus and diestrus. To investigate whether ENPP2 expression is affected by sex steroid hormone in the uterus of rats, we treated rats with 17β-oestradiol (E2), progesterone (P4), or E2 plus P4 from postnatal Day 14 to 16 in an immature rat model. Interestingly, ENPP2 mRNA and protein level expression was down-regulated by E2 in the uterus at oestrus, but not in the proestrus and diestrus, suggesting that the ENPP2 gene may be involved in uterine function during the oestrous cycle. Using immunohistochemistry with a specific antibody, we demonstrated the expression of ENPP2 protein localization in the uterus of rats during the oestrous cycle. In particular, ENPP2 was mainly located in the stromal cells in the uterine endometrium at the proestrus and oestrus cycles. The diestrous stage showed greater expression, and ENPP2 was mainly expressed in decidual cells. In conclusion, these results suggest that uterine ENPP2 induction is caused by steroid hormones during the oestrous cycle in rats, and this gene may be involved in reproductive function during a critical developmental stage of female rats.

Changes in ambient temperature and oxygenation during the proestrus do not affect duration, regularity and repeatability of the estrus cycle in female rats.

There are a lot of factors affecting the release of hormones from the anterior part of pituitary gland and their interactions with other parts of the endocrine, nervous and immune systems. The special significance of the proestrus phase of the estrous cycle of the rat, during which LH and FSH levels increase, followed by ovulation is known. The short length of the estrous cycle and the well recognized sequence of vaginal lavage cytology make it useful for investigating the influence of a stressful environment on the reproductive function. Short duration and mild changes in environmental conditions is considered as a factor analogous to psychological stress. The study was undertaken to determine the effects of a short duration change in the ambient temperature and oxygenation (30 minutes) on the proestrus phase of reproductive cycle and on the repeatability and regularity of phases of the reproductive cycle of Wistar strain rats. The animals were kept under standard conditions and had food and water available ad libitum. The climatic chamber with automatically adjustable and monitored internal parameters (temperature, oxygenation, humidity) was used to develop stress conditions. An estimation of the vaginal lavage using the microscope was done to determine the estrous cycle. The animals were divided into 6 groups. On the day of experiment: the control group (CG) stayed in the climatic chamber for 30 minutes (ambient temperature 21 degrees C, normoxia - 21% O(2)), the five test groups (TG - I - V) remained in the climatic chamber for 30 minutes, in the established environmental conditions (I - 21 degrees C, 10% O(2); II - 10 degrees C, 21% O(2); III - 10 degrees C, 10% O(2); IV - 35 degrees C, 21% O(2); V - 35 degrees C, 10% O(2)). During the following days after the experiment, a microscopic estimation of vaginal lavage was collected over again. There were no changes of duration and sequence of the present estrous cycle and repeatability of the next cycles. Our results indicate that short duration change in the ambient conditions do not cause a disturbance in the hypothalamo - pituitary - gonadal axis, although it can activate adaptation mechanisms of the organism.

Antiovulatory effect of a single injection of pure antiestrogen ZK 191703 at early stage of rat estrus cycle

The effects of ZK 191703 (ZK), a pure antiestrogen, on ovulation, follicle development and peripheral hormone levels were investigated in rats with 4-day estrus cycle and gonadotropin-primed immature rats in comparison to tamoxifen (TAM)-treatment. In adult rats, a single s.c. injection of ZK (5 mg/kg) or TAM (5 mg/kg) at an early stage of the estrus cycle (diestrus 9:00) inhibited ovulation, and was associated with suppression of the surge of preovulatory LH, FSH and progesterone. In rats treated with ZK or TAM at a late stage of the estrus cycle (proestrus 9:00), no inhibitory effects on ovulation, the gonadotropin and progesterone surge were detected. ZK treatment at diestrus 9:00, in contrast to TAM, increased the baseline LH level. When immature rats were treated with antiestrogens in the earlier stage of follicular development, 6 and 30 h but not 48 h or later after injection of gonadotropin (PMSG), ovulation was attenuated, associated with a lowered progesterone level. Unruptured preovulatory follicles were found in most of the ovaries from anovulatory animals treated with ZK or TAM. Antiestrogens, ZK and TAM administered at an early phase of the estrus cycle delay the follicular development functionally and inhibit ovulation in rats and suppression of the preovulatory progesterone surge.

Anxiety and plasma progesterone in estrus cycle in rats with opposite coping styles

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Baroreflex sensitivity varies during the estrus cycle of the rat

Baroreflex sensitivity (BRS) fluctuates during the menstrual cycle; it reaches its peak during the luteal phase, when gonadal steroids are elevated. However, whether BRS varies during the estrus cycle of the rat is unclear. To test this hypothesis, female rats (n=5) were instrumented for continuous telemetric (24 hr/day; 1000 Hz) measurement of blood pressure (BP) and were housed with a daily light:dark cycle of 12 hr:12 hr. After recovery (10 days), the estrus cycle was established by daily cytologic evaluation of vaginal smears for at least 2 cycles (~10 days). During the following 5–10 days, cardiovagal BRS (in ms/mmHg) was estimated using the sequence method, which selects spontaneous relationships between ramps in systolic BP and associated changes in pulse interval. On each day of the estrus cycle, BRS was increased during lights on (L‐on), compared to lights off (L‐off) (P<0.05). In addition, during L‐on, BRS was elevated on proestrus compared to estrus (1.77±0.11 vs. 1.59±0.08, P<0.05). During L‐off, BRS was increased during protestrus compared to both estrus and metestrus (1.54±0.06 vs. 1.39±0.15 and 1.29±0.04; P<0.05). To test if increases in gonadal hormones underlie the elevated gain on proestrus, rats (n=3) were studied for 4 consecutive days 1–2 weeks following ovariectomy (OVX). In OVX rats, no daily variations in BRS were observed (P>0.50). BRS on each of the 4 days during L‐on was: 1.37±0.20, 1.31±0.18, 1.37±0.20, 1.39±0.07; during L‐off: 1.23±0.06, 1.24±0.05, 1.24±0.01, 1.33±0.06. In summary, cardiovagal BRS fluctuates during the estrus cycle in rats and reaches its peak during proestrus. Because OVX eliminates this daily BRS variation, we conclude that changes in ovarian gonadal steroids mediate this BRS fluctuation. Supported by HL70962, AHA and Collins Fdn.

Oestrogen receptor α and β in female rat pituitary cells: An immunochemical study

Estradiol is a critical factor in the anterior pituitary secretory activity of mammalian females. Previous reports have demonstrated the presence of oestrogen receptor alpha (ERα) and beta (ERβ) in specific anterior pituitary cells from ovariectomized rats, as well as in the whole anterior pituitary at particular stages of the rat oestrous cycle. However, the ERα and ERβ distribution patterns in specific hormone producing cells of the anterior pituitary during the oestrous cycle remain to be clarified. The purpose of this study was to determine the cellular and subcellular distribution of both ER-subtypes during the rat oestrous cycle, using immunochemistry at light- and electron-microscope levels. ERα-immunoreactive (ir) cells mainly corresponded to PRL-ir cells and, to a lesser extent, to TSH-, FSH- and GH-ir cells. ERβ-ir cells corresponded to a few GH-, PRL- and FSH-ir cells, whichever the phase of the cycle. ERα-ir was found either in the cytoplasm and/or the nucleus, depending on the phase of the oestrous cycle, while ERβ-ir was always detected in the cytoplasm. Both ER-subtypes were immunoreactives inside the rough endoplasmic reticulum (RER), secretory vesicles (SV) and free in the cytosol. The highest number of ERα-ir cells was consistently found at pro-oestrus midday and the lowest at metaoestrous, while the number of ERβ-ir cells was low in all stages of the cycle. These results indicate that the genomic actions of oestrogen in the anterior pituitary cells during the oestrous cycle are mediated by ERα. However, the localization of ERα and ERβ in the RER and SV suggest a different translational and/or post-translational pathway, which could be involved in non-genomic mechanisms.

Role of hypothalamus nociceptin/orphanin FQ in pre-ovulatory luteinizing hormone surge of estrogen and progesterone-primed, ovariectomized rats

To investigate the role of hypothalamus nociceptin/orphanin FQ (OFQ) and its endogenous receptor, the opioid receptor-like1 receptor (ORL1 receptor) in the estrus cycle of female rats. Radioimmunoassay was used to detect the effect of the intracerebroventricular (icv) administration of OFQ and/or the ORL1 receptor antagonist [Nphe1]Nociceptin(1-13)NH2, that is, NC13 on luteinizing hormone (LH) levels of estrogen- and progesterone (EBP)-primed, ovariectomized (OVX) rats (EBP-primed OVX rats). RT-PCR, Western blotting, and immunohistochemistry techniques were adopted to observe the changes of OFQ and the ORL1 receptor in the pre-optic area (POA) and the medial basal hypothalamus (MBH) of the estrus cycle of female rat. Pre-ovulatory LH surges in EBP-primed, OVX rats were significantly reduced by icv administration of 20 and 200 nmol OFQ (P<0.05), and the effect of 20 nmol OFQ could be abolished by pretreatment with 20 nmol NC13. The OFQ mRNA level in the POA on pro-estrus was lowered markedly compared to diestrus and estrus (P<0.05), while the mRNA and protein levels of the ORL1 receptor showed no significant changes in the POA and MBH across the estrus cycle. Meanwhile, the number of OFQ-immunoreactive neurons in the medial POA, ventromedial hypothalamus, and the arcuate nucleus on pro-estrus was significantly decreased compared to diestrus and estrus (P<0.05). The inhibitory effect of OFQ on the LH surge of EBP-primed, OVX rats and its downregulation in POA and MBH on pro-estrus suggests that it might play a negative modulatory role in the estrus cycle.

Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle

During each oestrous cycle, the mammary gland is subject to changes in ovarian hormone levels. It responds with limited proliferation, differentiation and regression. To understand the processes resulting in these changes, particularly the regulation of cell death, we examined protein levels in mammary epithelium during the oestrous cycle of the Sprague-Dawley rat. Studies of serum hormone levels, vaginal smears, uterine weight and morphology, mammary gland morphology, proliferation and apoptotic indices, and protein levels during the stages of the Sprague-Dawley rat oestrous cycle were used to examine the response of mammary epithelium to the oestrous cycle. Proliferation of mammary epithelium was greater in diestrus and proestrus, while apoptosis was increased in metestrus and diestrus. Growth factor-, hormone- and anchorage-mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt 1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family members and proteins associated with apoptosis in mammary epithelium (TGFbeta3, pStat3) were increased during metestrus and diestrus. Decreases in growth factor, hormone and cell attachment survival signals corresponded with increased apoptosis during the second half of the oestrous cycle. The protein levels detected during oestrus suggest parallels to apoptosis in mammary involution.

Effects of Gonadal Steroid Hormones on Amylase Secretion in Pancreatic Lobules of Rats

Because functional changes of the pancreas during the ovarian cycle are not fully understood, effects of gonadal steroid hormones on pancreatic amylase content and secretion were investigated. The estrus cycle of female rats was confirmed by vaginal smear. To mimic the estrus or the diestrus, estradiol 17beta (25 microg/kg) or progesterone (50 mg/kg) was subcutaneously injected to ovariectomized rats once daily for 2 days. Amylase secretion of pancreatic lobules (approximately 6 mg wet weight) was induced by acetylcholine (10-8 approximately 10-4 M). In normal rats, pancreatic amylase content was not altered during the estrus cycle, whereas spontaneous amylase secretion of pancreatic lobules at the diestrus was significantly higher than that at the estrus. In ovariectomized rat, pancreatic amylase content was markedly reduced, which was restored by either estradiol 17beta or progesterone. Pancreatic lobules of ovariectomized rats spontaneously secreted amylase at the level identical to that at the estrus, which was elevated to the level at the diestrus by progesterone, but not affected by estradiol 17beta. In normal rats, acetylcholine induced amylase secretion much higher at the diestrus than at the estrus. In ovariectomized rats, the acetylcholine-induced amylase secretion was similar to that at the estrus, which was elevated by progesterone, but not affected by estradiol 17beta. We conclude from the above results that both estradiol 17beta and progesterone are necessary to maintain amylase content in the rat pancreas, but only progesterone exerts a stimulatory effect on spontaneous and stimulated amylase secretion in pancreatic lobules of rats.

Noradrenaline Release in the Medial Preoptic Area During the Rat Oestrous Cycle: Temporal Relationship with Plasma Secretory Surges of Prolactin and Luteinising Hormone

During the rat oestrous cycle, the afternoon of pro-oestrous is characterised by preovulatory surges of luteinising hormone (LH) and prolactin. On the afternoon of oestrous, a secretory surge of prolactin has also been reported. Because the medial preoptic area (MPOA) is known to regulate prolactin and LH secretory surges and noradrenaline has been demonstrated to stimulate these hormones release, we evaluated whether noradrenaline release in the MPOA was temporally associated with plasma prolactin and LH surges in cycling rats. During the 4 days of oestrous cycle, noradrenaline concentrations were determined in microdialysates from the MPOA, collected at 30-min intervals from 10.30 h to 19.00 h. Plasma prolactin and LH levels were measured in blood samples withdrawn hourly from 14.00 h to 19.00 h on pro-oestrous and from 13.00 h to 18.00 h on the other days of the cycle. On the afternoons of both pro-oestrous and oestrous, noradrenaline levels increased at 14.00 h and remained elevated until 16.30 h. Conversely, they were low and constant throughout metoestrous and dioestrous. Correlating with noradrenaline release in the MPOA, plasma prolactin surges occurred during the afternoons of both pro-oestrous and oestrous. On pro-oestrous, the afternoon LH surge was also preceded by the increase in MPOA noradrenaline whereas, during oestrous, LH secretion was low and unaltered. A temporal association between noradrenaline release and prolactin secretion suggests that noradrenergic neurotransmission in the MPOA regulates prolactin surges in female rats. Moreover, our data also suggest that MPOA noradrenaline requires specific conditions to physiologically regulate LH secretion, which seems to occur during the afternoon of pro-oestrous.

Effects of spirulina on the number of ovary mast cells in lead‐induced toxicity in rats

The present study investigated the protective effect of Spirulina against the lead-induced increase in mast cells in the ovary during the oestrous cycle of rats. In the ovary cortex and medulla of lead-exposed animals, there was a significant increase in the number of mast cells; however, when also treated with Spirulina, a decrease was observed. The number of mast cells when Spirulina (300 mg/kg) was used alone was not significantly different from that of the control group. These results indicate that Spirulina decreases the number of mast cells induced by lead in the cortex and medulla of rat ovary.

Some Pregnancy-Related Effects of Artemether in Laboratory Animals

Artemether, highly effective in multi-drug-resistant malaria is not routinely available for use in pregnancy due to the lack of adequate research data in animals and man. This study was therefore aimed at investigating some pregnancy-related effects of artemether. Artemether (1.5, 7.5 and 15 mg/kg i.p. daily for 7 days) did not produce changes in rat oestrous cycle. The drug did not prevent or prolong the rate of conception or parturition, cause pre-term delivery and affect litter size. Birth weight and growth rate of pups from artemether-pretreated dams were within the normal range. Artemether (48–480 µg/ml) had no agonist effect on the isolated uterine smooth muscles of both non-pregnant and pregnant rats and guinea pigs. However, the drug (24– 240 µg/ml) reduced oxytocin-induced contraction of uterine tissues concentration-dependently, particularly in pregnant uteri.

Estrus variation in anxiolytic-like effects of intra-lateral septal infusions of the neuropeptide Y in Wistar rats in two animal models of anxiety-like behavior

Anxiolytic-like effects of intra-lateral septal infusions of the neuropeptide Y (NPY) were assessed during several estrus phases in Wistar rats tested in two animal models of anxiety-like behavior. In a conflict operant test, results showed that during late proestrus, intra-lateral septal nuclei infusions of NPY (1.0 μg/μl, P < 0.05; 2.0 μg/μl, P < 0.05; 2.5 μg/μl, P < 0.05) increased the number of immediately punished responses. During metestrus–diestrus only the highest doses of NPY (2.5 μg/μl, P < 0.05) increased the number of immediately punished reinforcers. In the elevated plus-maze test, results showed that during late proestrus, intra-lateral septal nuclei infusions of NPY (1.0 μg/μl, P < 0.05; 2.0 μg/μl, P < 0.05) produced anxiolytic-like actions. During metestrus–diestrus only the highest doses of NPY (2.0 μg/μl, P < 0.05) produced anxiolytic-like actions. Neither NPY nor estrus phases significantly modified the number of closed arms entries in the elevated plus-maze test. It is concluded that anxiolytic-like effects of NPY vary within the estrus cycle in Wistar rats.