Cycling Female Rats Research Articles

Effects of troxerutin on pentylenetetrazol-induced convulsions during different stages of the estrus cycle in female rats

Effects of troxerutin on pentylenetetrazol-induced convulsions during different stages of the estrus cycle in female rats

The estrous cycle has no effect on incubation of methamphetamine craving and associated Fos expression in dorsomedial striatum and anterior intralaminar nucleus of thalamus

Relapse is a major challenge in treating drug addiction, and drug seeking progressively increases after abstinence, a phenomenon termed “incubation of drug craving”. Previous studies demonstrated both sex differences and an effect of estrous cycle in female rats in incubation of cocaine craving. In contrast, while incubation of methamphetamine craving is similar across sexes, whether estrous cycle plays a role in this incubation has yet to be fully addressed. Moreover, whether neural mechanisms underlying incubation of methamphetamine craving differ across estrous cycles is largely unknown. To address these gaps, we first compared methamphetamine self-administration, and methamphetamine seeking on both abstinence days 1 and 28 between male rats and female rats across the estrous cycle. Next, we examined neuronal activation associated with incubated methamphetamine seeking in dorsomedial striatum (DMS) and lateral portion of the anterior intralaminar nucleus of thalamus (AIT-L), two brain areas previously implicated in incubation of methamphetamine craving. We found no effect of sex or estrous cycle on methamphetamine self-administration and methamphetamine seeking on abstinence days 1 and 28. We also found no effect of sex or estrous cycle on the number of Fos-expressing cells in DMS or AIT-L following methamphetamine seeking test. Taken together, our results showed that methamphetamine self-administration and incubation of methamphetamine craving was not dependent on sex or estrous cycles under our experimental condition, and the role of DMS and AIT-L in incubation of methamphetamine craving may be similar across sexes and across estrous cycles in female rats.

Sleep- and sleep deprivation-related changes of vertex auditory evoked potentials during the estrus cycle in female rats

The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on auditory processing during the sleep–wake cycle and sleep deprivation. Vertex auditory evoked potentials (vAEPs) were evoked by single click tone stimulation and recorded during different stages of the estrus cycle and sleep deprivation performed in metestrus and proestrus in female rats. vAEPs showed a strong sleep-dependency, with the largest amplitudes present during slow wave sleep while the smallest ones during wakefulness. Higher amplitudes and longer latencies were seen in the light phase during all vigilance stages. The largest amplitudes were found during proestrus (light phase) while the shortest latencies were seen during estrus (dark phase) compared to the 2nd day diestrus baseline. High-amplitude responses without latency changes were also seen during metestrus with increased homeostatic sleep drive. More intense and faster processing of auditory information during proestrus and estrus suggesting a more effective perception of relevant environmental cues presumably in preparation for sexual receptivity. A 4-h sleep deprivation resulted in more pronounced sleep recovery in metestrus compared to proestrus without difference in delta power replacement suggesting a better tolerance of sleep deprivation in proestrus. Sleep deprivation decreased neuronal excitability and responsiveness in a similar manner both during metestrus and proestrus, suggesting that the negative consequences of sleep deprivation on auditory processing may have a limited correlation with the estrus cycle stage.

Relationship of induced thyroid gland disorders with fertility in cyclic female rats

Relationship of induced thyroid gland disorders with fertility in cyclic female rats

Cycle-dependent sex differences in expression of membrane proteins involved in cerebrospinal fluid secretion at rat choroid plexus

BackgroundFemale sex is a known risk factor of brain disorders with raised intracranial pressure (ICP) and sex hormones have been suggested to alter cerebrospinal fluid (CSF) dynamics, thus impairing ICP regulation in CSF disorders such as idiopathic intracranial hypertension (IIH). The choroid plexus (CP) is the tissue producing CSF and it has been hypothesized that altered hormonal composition could affect the activity of transporters involved in CSF secretion, thus affecting ICP. Therefore, we aimed to investigate if expression of various transporters involved in CSF secretion at CP were different between males and females and between females in different estrous cycle states. Steroid levels in serum was also investigated.MethodsFemale and male rats were used to determine sex-differences in the genes encoding for the transporters Aqp1 and 4, NKCC1, NBCe2, NCBE; carbonic anhydrase enzymes II and III (CA), subunits of the Na+/K+-ATPase including Atp1a1, Atp1b1 and Fxyd1 at CP. The estrous cycle stage metestrus (MET) and estrous (ES) were determined before euthanasia. Serum and CP were collected and subjected to RT-qPCR analysis and western blots. Serum was used to measure steroid levels using liquid chromatography tandem mass spectrometry (LC–MS/MS).ResultsSignificant differences in gene expression and steroid levels between males and ES females were found, while no differences were found between male and MET females. During ES, expression of Aqp1 was lower (p < 0.01) and NKCC1 was higher in females compared to males. CAII was lower while CAIII was higher in ES females (p < 0.0001). Gene expression of Atp1a1 was lower in ES compared to male (p = 0.0008). Several of these choroidal genes were also significantly different in MET compared to females in ES. Differences in gene expression during the estrus cycle were correlated to serum level of steroid hormones. Protein expression of AQP1 (p = 0.008) and CAII (p = 0.035) was reduced in ES females compared to males.ConclusionsThis study demonstrates for the first time that expression at CP is sex-dependent and markedly affected by the estrous cycle in female rats. Further, expression was related to hormone levels in serum. This opens a completely new avenue for steroid regulation of the expression of CSF transporters and the close link to the understanding of CSF disorders such as IIH.

Progesterone-loaded solid lipid nanoparticles for use in the regulation of the estrous cycle in female rats

Progesterone-loaded solid lipid nanoparticles for use in the regulation of the estrous cycle in female rats

Effects of sex and estrous cycle on intravenous oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats.

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a fixed-ratio 1 schedule of reinforcement in daily 2-h sessions, and a dose-response function was subsequently determined (0.003-0.03 mg/kg/inf). In experiment 2, a separate group of adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone for 8 sessions, followed by 0.01 mg/kg/inf oxycodone for 10 sessions. Responding was then extinguished, followed by sequential footshock-induced and cue-induced reinstatement tests. In the dose-response experiment, oxycodone produced a typical inverted U-shape function with 0.01 mg/kg/inf representing the maximally effective dose in both sexes. No sex differences were detected in the reinforcing efficacy of oxycodone. In the second experiment, the reinforcing effects of 0.01-0.03 mg//kg/inf oxycodone were significantly attenuated in females during proestrus/estrus as compared to metestrus/diestrus phases of the estrous cycle. Neither males nor females displayed significant footshock-induced reinstatement of oxycodone seeking, but both sexes exhibited significant cue-induced reinstatement of oxycodone seeking at magnitudes that did not differ either by sex or by estrous cycle phase. These results confirm and extend previous work suggesting that sex does not robustly influence the primary reinforcing effects of oxycodone nor the reinstatement of oxycodone-seeking behavior. However, our findings reveal for the first time that the reinforcing efficacy of IV oxycodone varies across the estrous cycle in female rats.

The impact of motherhood on anxiety symptoms over the menstrual cycle: A translational approach in female rats and women

Fluctuating sex hormones across the estrous/menstrual cycle in female rats and women are associated with changes in anxiety, which could contribute to the maintenance of anxiety disorders. Pregnancy causes long-term changes in sex hormonal fluctuations, yet extant research has focused on reproductively inexperienced females. This study employed a cross-species approach to assess whether the impact of estrous/menstrual cycle on anxiety differs pre- versus post-motherhood. Naturally cycling virgin rats (n=14) and mother rats (n=18) were tested twice on the open field maze, light-dark box, and elevated plus maze to measure anxiety-like behaviour; during metestrus (low sex hormones) and proestrus (high sex hormones). In addition, a human community sample of naturally cycling non-mothers (n=35) and mothers (n=28) completed the Patient Health Questionnaire-4 at three timepoints; during the early-follicular phase (low sex hormones), ovulation (high sex hormones), and mid-luteal phase (high sex hormones). Replicating past research, virgin rats showed higher anxiety-like behaviour during metestrus versus proestrus. In contrast, mother rats showed similar anxiety-like behaviour irrespective of estrous phase. Replicating past research in humans, non-mothers reported higher anxiety and depression during the early-follicular phase compared to other menstrual phases. In contrast, mothers reported similar anxiety and depression irrespective of menstrual phase. Changes in anxiety coincident with cycling hormones is an evolutionary conserved feature of the estrous/menstrual cycle in rats and women, which may be mitigated post-motherhood in both species. These findings highlight the importance of considering reproductive status in studies on anxiety in females.

The impact of the ovarian cycle on anxiety, allopregnanolone, and corticotropin releasing hormone changes after motherhood in female rats and women

Fluctuations in ovarian steroids across the estrous and menstrual cycle in female rats and women, respectively, are associated with changes in anxiety. Pregnancy causes long-term changes to ovarian hormone release, yet research on estrous- and menstrual-related changes in anxiety has focused on reproductively inexperienced females. Therefore, this study assessed whether the impact of estrous and menstrual cycles on anxiety differs pre- versus post-motherhood in female rats (n = 32) and a community sample of women (n = 63). Estrous cycle phase altered anxiety-like behavior in virgin rats, but had no effect in age-matched mother rats tested 1-month post-weaning. In humans, menstrual cycle phase was associated with ecological momentary assessed anxiety and mood in non-mothers, but not mothers; although, the menstrual cycle × reproductive status interaction for anxiety, but not mood, was rendered non-significant with age and cycle length as covariates. These findings suggest that changes in anxiety coincident with cycling hormones is an evolutionarily conserved feature of the estrous and menstrual cycle in rats and women, which is mitigated following motherhood in both species. We identified several potential mechanisms for the observed dissociation in estrous cycle effects on anxiety. Compared to virgin rats, mother rats had a lower peak and blunted decline in circulating allopregnanolone during proestrus, upregulated GABAA receptor subunit (α1, α2, α5, α4, ß2) mRNA in the ventral hippocampus, and altered corticotropin-releasing hormone mRNA across the estrous cycle in the basolateral amygdala. Together, these findings suggest that the mechanisms underlying anxiety regulation undergo fundamental transformation following pregnancy in female rats and humans.

NTS, NTSR1 and ERs in the Pituitary-Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment.

The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus-pituitary-gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life.

Expression of phoenixin-14 and nesfatin-1 in the hypothalamo–pituitary–gonadal axis in the phases of the estrous cycle

Phoenixin-14 (PNX-14) and nucleobindin 2 (NUCB2)/nesfatin-1 are regulatory neuropeptides expressed in the hypothalamus. These neuropeptides can be effective in hormonal regulation of the hypothalamo–pituitary–gonadal (HPG) axis and reproductive functions. In the present study, the distribution of PNX-14 and NUCB2/nesfatin-1 in the hypothalamus, pituitary, ovary, and uterus tissues during the phases of the estrous cycle in female rats was investigated. Eighteen Wistar Albino rats determined among animals showing regular estrous cycle by vaginal smear method were divided into three groups: proestrus (Group I), estrus (Group II) and diestrus (Group III). Serum gonadotropin-releasing hormone (GnRH), plasma PNX-14, and NUCB2/nesfatin-1 concentrations were the highest, moderate, and lowest in estrus, diestrus, and proestrus phases, respectively. PNX-14 immunoreactivity in the supraoptic and arcuate nuclei of the hypothalamus and NUCB2/nesfatin-1 immunoreactivity in the paraventricular nuclei were particularly evident in the estrus phase. These neuropeptide immunoreactivities were decreased in different cells of anterior pituitary during proestrus compared with those during estrus and diestrus. PNX-14 immunoreactivity in the ovary, especially during the estrus phase, was diffuse and intense in the granulosa and luteal cells and oocytes, and it was few and weak in theca cells. In addition, NUCB2/nesfatin-1 immunoreactivity was abundant and strong in granulosa and luteal cells, theca and interstitial cells, and oocytes during estrus. In the estrus phase, PNX-14 immunoreactivity was strong in the glandular epithelial cells and stromal cells of the endometrium, also NUCB2/nesfatin-1 immunoreactivity was strong in the epithelial and glandular epithelial cells. As a result, when the estrous cycle was evaluated, it was concluded that the changes in the distribution of PNX-14 and NUCB2/nesfatin-1 at all phases were related to GnRH and that these neuropeptides showed the highest immunoreactivity especially in the HPG axis and uterus tissues of estrus rats.

Gonadotropin profile in experimentally induced hypothyroid and hyperthyroid cyclic female rats

The current study examined the association of thyroid disorders with reproductive dysfunction by determining its effect on gonadotropin secretion in cyclic female rats. Sixty cyclic females were assigned to three groups (20 each) and supplemented, for 30 days plus two consequent estrous cycles, with drinking water (control), methimazole in drinking water (0.02% w/v) (hypothyroid group), and thyroxine in drinking water (0.002% w/v) and gastric gavage of 200 μg/kg body weight (hyperthyroid group). At late proestrus, ten females from each group (for each cycle) were anesthetized and dissected. Blood samples were obtained to assess thyroid-stimulating hormone, free and total triiodothyronine, free and total thyroxin, follicle-stimulating hormone, luteinizing hormone, and prolactin concentrations. Ovarian and pituitary tissue samples were obtained for molecular analysis of ovarian thyroid receptor genes and pituitary TSH, FSHβ, and LHβ genes. In comparison with control, the Hypo group revealed increased serum concentrations of TSH and PRL and the expression levels of pituitary TSH and ovarian TRsTRs genes and significant decrease of FT3, TT3, FT4, TT4, FSH, and LHLH concentrations and the expression levels of pituitary FSHβ and LHβ genes. In contrast, the Hyper group showed increased serum FT3, TT3, FT4, TT4, and LHLH concentrations and the expression levels of pituitary LHβ and ovarian TRsTRs genes and decreased serum TSH FSH and PRL concentrations and pituitary FSHβ and TSH gene expression levels. It is concluded that thyroid dysfunction is associated with altered serum gonadotropin secretion and reproductive failure.

Antifertility activity of Momordica dioica and Lagerstroemia speciosa in experimental rats

Agents that control fertility are termed as antifertility agents or oral contraceptives. Many plant-based products have the antifertility potential which need to be explored.The present study therefore was undertaken to evaluate possible antifertility effects of hydroalcoholic extract of fruits of (HAEMD) and aqueous extract of leaves of (AELS) in experimental rats. Experiments were carried using wistar rats of either sex. Animals were administered with different doses of HAEMD and AELS (250, and 350 mg/kg, p. o) for 30 days. The body weight and reproductive organs weights for male (Testis) and for female (Uterus) were analyzed. Sperm count and Sperm motility was determined in male rats by manually. Testosterone in male and progesterone levels in female rats were checked. Effect of both extracts on Estrous cycle in female rats were checked. Section of testis were taken for histopathological study. The effect of the extract on male rats showed decreased testis weight, reduced sperm count and motility as compared to control animals. The blood testosterone level in male rats was reduced in treatment groups. The testicular histology was altered as compared to control male rats. In female animals, extracts showed antiovulatory activity, alteration in estrous cycle, decreased uterus weight and serum progesterone levels. It is concluded that HAEMD and AELS are effective as antifertility plants for both male and female rats.

Aging-related changes in metabolic indicators in female rats and their management with Tinospora cordifolia.

Conflicting reports of HRT necessitates exploration of therapeutic interventions with the least side effects to preserve metabolic homeodynamics in women later in life. The current study was designed to elucidate the cumulative effects of aging and/or high fat diet (HFD) on some metabolic indicators and their management by Tinospora cordifolia stem powder (TCP) using middle-aged acyclic and young adult cyclic female rats as the model system. Animals were fed on either normal chow or HFD supplemented with or without TCP. Blood and liver tissue were collected for biochemical, and histological studies as well as for expression of proteins regulating lipid metabolism. Animals fed with TCP supplemented normal chow feed showed bodyweight management over 12-weeks despite their high feed and calories intake compared to young and age-matched controls as well as HFD-fed animals. TCP dose used was not toxic and rather prevented age-associated liver dysfunctions and ameliorated dyslipidemia and oxidative stress, normalized blood glucose, insulin, leptin, and secretary pro-inflammatory cytokines. Further, bodyweight management effect of TCP was observed to target AMPK signalling pathway as the mediator of lipogenesis, sterol biosynthesis, lipolysis, and β-oxidation of fatty acids. These findings suggest that TCP supplementation in diet may be a potential interventional strategy to ameliorate aging-associated hepatic and metabolic dysfunctions and to promote healthy aging.

L-Carnitine alleviates hepatic and renal mitochondrial-dependent apoptotic progression induced by letrozole in female rats through modulation of Nrf-2, Cyt c and CASP-3 signaling

Letrozole (LTZ) is a non-steroidal aromatase inhibitor that is commonly used in breast cancer therapy. It has several side effects that might lead to the drug's cessation and data of LTZ's potential adverse effects on the hepatorenal microenvironment was conflicting. In addition, searching for therapeutic interventions that could modulate its adverse effects will be very beneficial. So, this study aims to determine the impact of LTZ on the hepatorenal microenvironment in cyclic female rats with a proposed regulatory role of L-Carnitine (LC) supplementation giving molecular insights into its possible mechanism of action. LTZ (1 mg/kg using 0.5% carboxy methyl cellulose as a vehicle for 21 consecutive days orally) to assess its impact on hepatorenal microenvironment. After treatment with LC (100 mg/kg orally) for 14 days, hepatorenal redox state (lipid peroxides (MDA), reduced glutathione (GSH) and catalase enzyme (CAT)), as well as relative gene expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), cytochrome-c (Cyt c) and caspase-3 (CASP-3) were evaluated. Histopathological examination and immunohistochemical staining of CASP-3 in both liver and kidney were done. LTZ altered hepatic and renal functions. Relative gene expression of hepatorenal Nrf-2, Cyt c and CASP-3 as well as redox state revealed significant deterioration. Also, the liver and kidney tissues showed several micromorphological changes and intense reaction to CASP-3 upon immunohistochemical staining. It can be concluded that LC alleviates LTZ induced hepatorenal oxidative stress (OS) and mitochondrial-dependent apoptotic progression through modulation of Nrf-2, Cyt c, and CASP-3 signaling in female rats.

Naringenin and morin reduces insulin resistance and endometrial hyperplasia in the rat model of polycystic ovarian syndrome through enhancement of inflammation and autophagic apoptosis.

Polycystic Ovary Syndrome (PCOS) is a gynecologic disorder with unsatisfactory treatment options. Hyperandrogenism and insulin resistance (IR) are two symptoms of PCOS. The majority of PCOS patients (approximately 50% to 70%) have IR and moderate diffuse inflammation of varying degrees. We investigated in-vitro and in-vivo effects of naringenin, morin and their combination on PCOS induced endometrial hyperplasia by interfering with the mTORC1 and mTORC2 signaling pathways. The vaginal smear test ensured the regular oestrous cycles in female rats. Serum cytokines (TNF-α and IL-6) were assessed using the ELISA test, followed by in-vivo and in-vitro determination of prominent gene expressions (mTORC1and C2, p62, LC3-II, and Caspase-3 involved in the inflammatory signaling mechanisms through RT-PCR, western bloting, or immunohistochemical analysis. In addition, the viability of naringenin or morin treated cells was determined using flow cytometry analysis. The abnormal oestrous cycle and vaginal keratosis indicated that PCOS was induced successfully. The recovery rate of the oestrous cycle with treatments was increased significantly (P<0.01) when compared to the PCOS model. Narigenin, morin, or a combination of the two drugs substantially decreased serum insulin, TNF-α, IL-6 levels with improved total anti-oxidant capacity and SOD levels (P<0.01). Treatments showed suppression of HEC-1-A cells proliferation with increased apoptosis (P<0.01) by the upregulation of Caspase-3 expression, followed by downregulation of mTORC, mTORC1, and p62 (P<0.01) expressions with improved LC3-II expressions (P<0.05) respectively. The histological findings showed a substantial increase in the thickness of granulose layers with improved corpora lutea and declined the number of cysts. Our findings noticed improved inflammatory and oxidative microenvironment of ovarian tissues in PCOS treated rats involving the autophagic and apoptotic mechanisms demonstrating synergistic in-vitro and in-vivo therapeutic effects of treatments on PCOS-induced endometrial hyperplasia.

Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone.

Orofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone’s activity in the trigeminal system. Progesterone has been reported to exert protective effects through actions at intracellular progesterone receptors (iPR), membrane-progesterone receptors (mPR), or sigma 1 receptors (Sig-1R). Of these, the iPR and Sig-1R have been reported to have a role in pain. Progesterone can also have antinociceptive effects through its metabolite, allopregnanolone. Two enzymes, 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD), are required for the metabolism of progesterone to allopregnanolone. Both progesterone and allopregnanolone rapidly attenuate pain sensitivity, implicating action of either progesterone at Sig-1R and/or conversion to allopregnanolone which targets GABAA receptors. In the present study, we investigated whether Sig-1 Rs are expressed in nociceptors within the trigeminal ganglia of cycling female rats and whether the two enzymes required for progesterone metabolism to allopregnanolone, 5α-reductase and 3α-hydroxysteroid dehydrogenase, are also present. Adult female rats from each stage of the estrous cycle were rapidly decapitated and the trigeminal ganglia collected. Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.

GABA A /Benzodiazepine Receptor Complex in the Dorsal Hippocampus Mediates the Effects of Chrysin on Anxiety-Like Behaviour in Female Rats.

Systemic injections of the flavonoid chrysin (5,7-dihydroxyflavone) exert anxiolytic-like effects in ovariectomised and cycling female rats through actions on gamma-aminobutyric acid-A (GABAA) receptors; however, it is unknown if chrysin directly acts on brain structures that are involved in regulating emotional processes, such as the hippocampus. The present study evaluated the effects of intrahippocampal microinjections of 0.25, 0.5, and 1 μg of chrysin on anxiety-like behaviour in the elevated plus maze (EPM) and locomotor activity test (LAT) in female rats in proestrus and dioestrus. Similar doses of the neurosteroid allopregnanolone were used as a reference GABAergic anxiolytic drug. The participation of the GABAA/benzodiazepine receptor complex was evaluated by administering the antagonists picrotoxin, bicuculline and flumazenil. In proestrus, 0.5 and 1 μg of chrysin and allopregnanolone induced anxiogenic-like behaviour. In dioestrus, chrysin, and allopregnanolone (0.5 μg) induced anxiolytic-like effects. Picrotoxin, bicuculline and flumazenil prevented the effects of chrysin and allopregnanolone in both proestrus and dioestrus. None of the treatments significantly affected locomotor activity. These results indicate that the GABAA/benzodiazepine receptor complex in the dorsal hippocampus regulates the effects of chrysin on anxiety-like behaviour, similar to the actions of allopregnanolone. The divergent effects of treatments across the oestrous cycle phases suggest complex interactions between GABAA receptors and compounds with an anxiolytic potential.

Influence of genistein and diadizine on regularity of estrous cycle in cyclic female Wistar rat: interaction with estradiol receptors and vascular endothelial growth factor.

Isoflavones are estrogenic compounds that exist in soy, clover, and peanuts. They are selective estrogen receptor modulators. The study was planned to explain the interactions of isoflavones with estrogen receptors alpha (ERα), beta (ERβ), and vascular endothelial growth factor (VEGF) expressions in ovarian and uterine tissues during different stages of the estrous cycle of regular cyclic female Wistar rats. Thirty-two regular cyclic females were divided equally into control group: fed casein-based diet and isoflavones group: fed casein-based diet and gavaged 50 mg/kg/day soy isoflavones extract 40%. The regularity of estrus cycles was monitored. Final body weight (FBW), weight gain (BWG), and ovarian and uterine weights were estimated. Histopathology and immunohistochemistry for ERα, Erβ, and VEGF in ovarian and uterine tissues were performed. All females (100%, n = 16) in control group showed regularity in estrous cycle compared to 62.5% (n = 10) in isoflavones group. Estrus and diestrus phases revealed prolongation and shortening in isoflavones rats than control, respectively. Nonsignificant variation was noted in the duration of the whole cycle of both groups. FBW and BWG significantly decreased however, ovarian and uterine weights increased significantly in all estrous phases of isoflavones group than control. Histopathology demonstrated an increase in number of follicles/ovaries besides, hyperplasia and proliferation of luminal epithelium with hydropic degeneration in the isoflavones group. Also, uterine connective tissue stroma showed edema in the isoflavones group during all estrous phases. Immunostaining percentages of ERα, Erβ, and VEGF protein expression were significantly elevated in the isoflavones group during all estrous phases. Isoflavones induced irregularity of the estrous cycle that was encountered by increased and altered ERα, Erβ, and VEGF expressions in ovarian and uterine tissues.

Increase in sexual motivation throughout adolescence in the cycling female rat.

Sexual behavior in the female rat is a highly motivated behavior first displayed during adolescence, a developmental period when neural circuits underlying motivation are not mature. This study characterizes the natural development of sexual motivation and behavior of female rats. We compared the incentive value of the male for mid-adolescent (PNDs:39-43), late adolescent (PNDs:49-53), and adult (PNDs:90-115) cycling females, using a male-female preference task and an ultrasonic vocalization emission test following exposure to a male or female stimulus animal. Furthermore, display of sexual and social behaviors during an interaction with a male or a nonreceptive female was assessed. Mid-adolescent rats exhibited a reduced preference for the male than adults and performed less attempts to access the male. Unlike late adolescent and adult females, mid-adolescent rats did not increase their ultrasonic vocalization emission after interacting with a male relative to a female. Although most of the sexual behavior did not differ between groups, mid-adolescent females showed lower lordosis magnitude and higher levels of play and social investigation during a sexual interaction, giving rise to a unique behavioral profile. Present results indicate that the sexual behavior repertoire is fully displayed by mid-adolescence, but sexual motivation is low and increases into late adolescence.