Estradiol and neuropeptide Y (intra-lateral septal) reduce anxiety-like behavior in two animal models of anxiety

Anxiolytic-like effects of intra-lateral septal nuclei (LSN) infusions of the neuropeptide Y (NPY) alone or combined with estradiol benzoate were assessed in ovariectomized Wistar rats in two animal models of anxiety-like behavior. In a conflict test, immediately punished responses were assessed: 17-beta-estradiol (50.0microg/rat, P<0.05) plus vehicle (intra-LSN) or intra-LSN infusions of NPY (2.5microg/microl, P<0.05; 3.0microg/mul, P<0.05) plus vehicle (systemic route) or the combination of subthreshold doses of 17-beta-estradiol (25.0microg/kg) plus intra-LSN infusions of NPY (2.0microg/mul, P<0.05) increased the amount of immediately punished reinforcers. In the elevated plus-maze test several spatial-temporal variables were evaluated: 17-beta-estradiol (50.0microg/kg, P<0.05) plus vehicle (intra-LSN) or intra-LSN infusions of NPY (2.5microg/mul, P<0.05; 3.0microg/mul, P<0.05) plus vehicle (systemic route) or the combination of subthreshold doses of 17-beta-estradiol (25.0microg/kg) plus intra-LSN infusions of NPY (2.0microg/mul, P<0.05) produced anxiolytic-like actions without affecting locomotion. It is concluded that estradiol or NPY may produce anxiolytic-like actions and that subthreshold doses of estradiol and subthreshold doses of NPY when combined produced anxiolytic-like actions.     

Fluoxetine, 17-β estradiol or folic acid combined with intra-lateral septal infusions of neuropeptide Y produced antidepressant-like actions in ovariectomized rats forced to swim

Folic acid is antidepressant, either alone or combined with several antidepressant drugs. However, the antidepressant-like actions of folic acid combined with intra-lateral septal (LSN) infusions of neuropeptide Y (NPY) in the forced swimming test (FST) have not been tested before. Thus, systemic injections of fluoxetine (20.0 mg/kg, P < 0.05; s.c.) or 17-β estradiol (10.0 μg/rat, P < 0.05; s.c.) or oral administrations of folic acid (50.0 mg/kg, P < 0.05; 75.0 mg/kg, P < 0.05) or NPY intra-LSN (3.0 μg, P < 0.05; 3.5 μg, P < 0.05) reduced immobility of ovariectomized Wistar rats. Subthreshold doses of: folic acid (25.0 mg/kg) or 17-β estradiol (5.0 μg/rat, P < 0.05) or fluoxetine (15.0 mg/kg, P < 0.05; s.c.) combined with subthreshold doses of NPY (2.5 μg/rat, P < 0.05; intra-LSN) and these combinations produced antidepressant-like actions; which were canceled by BIBP 3226 (a NPY-Y1 receptor antagonist). It is concluded that folic acid produced antidepressant-like effects probably through the participation of the NPY Y1 receptors found in the lateral septal nuclei.     

Fluoxetine, 17-β estradiol or folic acid combined with intra-lateral septal infusions of neuropeptide Y produced antidepressant-like actions in ovariectomized rats forced to swim

Folic acid is antidepressant, either alone or combined with several antidepressant drugs. However, the antidepressant-like actions of folic acid combined with intra-lateral septal (LSN) infusions of neuropeptide Y (NPY) in the forced swimming test (FST) have not been tested before. Thus, systemic injections of fluoxetine (20.0 mg/kg, P < 0.05; s.c.) or 17-β estradiol (10.0 μg/rat, P < 0.05; s.c.) or oral administrations of folic acid (50.0 mg/kg, P < 0.05; 75.0 mg/kg, P < 0.05) or NPY intra-LSN (3.0 μg, P < 0.05; 3.5 μg, P < 0.05) reduced immobility of ovariectomized Wistar rats. Subthreshold doses of: folic acid (25.0 mg/kg) or 17-β estradiol (5.0 μg/rat, P < 0.05) or fluoxetine (15.0 mg/kg, P < 0.05; s.c.) combined with subthreshold doses of NPY (2.5 μg/rat, P < 0.05; intra-LSN) and these combinations produced antidepressant-like actions; which were canceled by BIBP 3226 (a NPY-Y1 receptor antagonist). It is concluded that folic acid produced antidepressant-like effects probably through the participation of the NPY Y1 receptors found in the lateral septal nuclei.     

Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze

Central administration of neuropeptide Y (NPY) produces anxiolytic-like behavioral effects in rat models of anxiety. Because previous evidence has suggested a relationship between NPY and corticotropin-releasing factor (CRF) in the brain, we have focused on the interaction of these neuropeptide systems in emotional responsiveness to stressful stimuli. Intracerebroventricular administration of CRF produced a marked response suppression in an operant incremental shock conflict paradigm. NPY [(1 microg, intracerebroventricularly (i.c.v.)] significantly antagonized the response-suppressing effects of CRF (0.75 microg, i.c.v.) on punished responding in the conflict test at doses that produced little or no behavioral effect when administered alone. Central administration of the CRF antagonist [D-Phe(12), Nle(21,38),C(alpha) MeLeu(37)]CRF (D-Phe CRF(12-41)) alone did not alter punished or unpunished responding in the conflict test. However, pretreatment with the CRF antagonist before a subthreshold dose of NPY (1 microg, i.c.v.) produced a significant potentiation of the release of punished responding relative to NPY alone and untreated controls. NPY also antagonized the "anxiogenic-like" behavioral effects of CRF in the elevated plus maze. These findings support the hypothesis that NPY and CRF may reciprocally modulate an animal's behavioral response to stressful stimuli.     

Rubimetide (Met-Arg-Trp) derived from Rubisco exhibits anxiolytic-like activity via the DP1 receptor in male ddY mice

In this study, we found that Met-Arg-Trp (rubimetide), which had been isolated as a hypotensive peptide from a pepsin-pancreatin digest of spinach ribulose bisphosphate carboxylase/oxygenase (Rubisco), has anxiolytic-like activity in the elevated plus-maze test at a dose of 0.1mg/kg (i.p.) or 1.0mg/kg (p.o.) in mice with p<0.01 and p<0.05, respectively. The anxiolytic-like activity of rubimetide (0.1mg/kg, i.p.) was blocked by BW A868C (60microg/kg, i.p.), an antagonist for the DP1 receptor, suggesting the anxiolytic-like activity of rubimetide is mediated by prostaglandin D2 and the DP1 receptor.     

Anxiolytic-like effect of the selective neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze

The involvement of Neuropeptide Y (NPY) in the pathophysiology of mood disorders has been suggested by clinical and preclinical evidence. NPY Y1 and Y2 receptors have been proposed to mediate the NPY modulation of stress responses and anxiety related behaviors. To further investigate the role of Y2 receptors in anxiety we studied the effect of BIIE0246, a selective Y2 receptor antagonist, in the elevated plus-maze test. Rats treated with 1.0 nmol BIIE0246 showed an increase in the time spent on the open arm of the maze. In addition, to study the effects of the Y2 antagonism on NPY protein level, NPY-like immunoreactivity was measured in different brain regions following treatment with BIIE0246, but no statistically significant effects were observed. These results suggest that BIIE0246 has an anxiolytic-like profile in the elevated plus-maze.     

Involvement of 5-HT1A receptors in passive avoidance learning in intact and ovariectomized female rats

The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) injected for 14 days alone or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on passive avoidance performance (PAR) and on behavior in the open field test in adult intact and ovariectomized (OVX) female rats. Administration of 5-HT1A receptor antagonist NAN-190 alone significantly improved PAR (p<0.05) in intact females with proestrus and estrus and in OVX females. Administration of 5-HT1A receptor agonist 8-OH-DPAT alone or in combination with 17beta-estradiol significantly (p<0.05) improved PAR in OVX rats and failed to normalize PAR in intact rats with proestrus and estrus. Results of the work specify the involvement of 5-HT1A receptors in the mechanisms of passive avoidance learning in OVX female rats.     

Effects of intra-amygdala injection of GABA(A)-receptor agonist and antagonist on behavior of active and passive rabbits in negative emotional situations

The effects of right-side or left-side intra-amygdala injections of the GABA(A)-receptor agonist muscimol hydrobromide (0.1 microg/1 microl) and antagonist bicuculline methiodide (0.05, 0.1, 0.5 microg/1 microl) on the behavior of active and passive rabbits were studied in open field, light-dark test and during presentation of emotionally significant stimuli. The effect of compounds injection was differed in active and passive rabbits. The active rabbits were more sensitive to bicuculline injection and the passive rabbits to muscimol administration. Bicuculline induced anxiolytic-like effects on the active animals in open field, light-dark test and motor-activating effects during emotionally significant stimuli. Muscimol induced anxiolytic-like effects on the passive rabbits and sedative effects on the both groups of rabbits. The differences in effectiveness of right-side and left-side intra-amygdala injections on behavior of rabbits were revealed: more powerful changes were during injection of bicuculline in left and muscimol in right amygdala. Anxiolytic-like effects were revealed during injection of bicuculline into left amygdala of active rabbits and muscimol into right amygdala of passive rabbits. These findings indicate that there are individual-typological and interhemispheric differences in functioning of GABAergic system of amygdala.     

Variations in concentration of oxytocin and vasopressin in the paraventricular nucleus of the hypothalamus during the estrous cycle in rats

Oxytocin (OT) and arginine-8-vasopressin (AVP) were measured by radioimmunoassay in micropunched hypothalamic neurosecretory nuclei of estrous cycling female Sprague-Dawley rats. In the paraventricular nucleus (PVN): the concentration (pg/microgram protein) of OT was significantly higher in rats in diestrus than during proestrus, estrus, or metestrus, while the concentration during metestrus was significantly greater than in proestrus and estrus; the concentration of AVP was significantly lower in animals in estrus than during the other three stages; because the paraventricular OT levels dropped before proestrus, the AVP/OT ratio was significantly greater in animals in proestrus than in diestrus, metestrus, and estrus. In the supraoptic nucleus (SON) a similar trend was noted: the concentration of OT was highest during diestrus, and AVP was lowest during estrus, though neither was significantly different from other stages. Because the OT and AVP cycles in the SON were asynchronous, the ratio of AVP to OT was significantly higher in proestrus than in metestrus or diestrus and significantly greater in estrus than during diestrus. In contrast to these two areas, peptide concentrations did not vary significantly across the estrous cycle in other sites of nonapeptide synthesis, i.e. the anterior commissural nucleus (ACN) and the suprachiasmatic nuclei (SCN).     

Anxiolytic-like effects of sinapic acid in mice

Sinapic acid is a phenylpropanoid compound and is found in various herbal materials and high-bran cereals. With the exception of its antioxidant activities, the pharmacological properties of sinapic acid have been rarely reported. The purpose of this study was to characterize the putative anxiolytic-like properties of sinapic acid using an elevated plus-maze (EPM) and hole-board test. Control mice were orally treated with an equal volume of vehicle (10% Tween 80 solution), and positive control mice were treated with diazepam (1 mg/kg, i.p.). Sinapic acid (4 mg/kg, p.o.) significantly increased the percentages of time spent in the open arms of the EPM test (P<0.05). In the hole-board test, sinapic acid also significantly increased the number of head-dips at 4 mg/kg (P<0.05). In addition, the anxiolytic-like properties of sinapic acid examined in the EPM test were blocked by flumazenil or bicuculline, which are GABA(A) antagonists. Moreover, sinapic acid markedly potentiated GABA current in single cortical neurons in a dose-dependant manner, and reactive I(GABA) increased to 1.8 times at 1 muM of sinapic acid. These results suggested that sinapic acid is a prominent anxiolytic agent, and that its anxiolytic-like effects are mediated via GABA(A) receptors and potentiating Cl(-) currents.     

Naloxone blocks 'anxiolytic' effects of neuropeptide Y

Intracerebroventricular injection of neuropeptide Y (NPY) produces potent 'anxiolytic' effects in animal models of anxiety. Administration of opioid receptor antagonists suppresses NPY-induced food intake and thermogenesis. The present study examined whether the opiate antagonist naloxone would also suppress the 'anxiolytic' effects of neuropeptide Y. Following training and stabilization of responding in an operant conflict model of anxiety, rats were injected with either NPY or diazepam. Both NPY (veh., 2, 4, 6 microg, i.c.v.) and chlordiazepoxide (veh., 2, 4, 6 mg/kg, i.p.) produced a dose-dependent increase in punished responding in the conflict test. The 'anxiolytic' effects of NPY were not blocked by the administration of flumazenil (3, 6, 12 mg/kg, i.p.). The administration of naloxone (0.25-2.0 mg/kg, s.c.) antagonized the effects of NPY. Central administration of the selective mu opiate antagonist CTAP (1 microg, i.c.v.) partially blocked NPY-induced conflict responding. These results support the hypothesis that NPY may play an important role in experimental anxiety independent of the benzodiazepine receptor and further implicate the opioid system in the behavioral expression of anxiety.     

The effects of a low dose of cabergoline on induction of estrus and pregnancy rates in anestrous bitches

This is the first report of successful induction of normal estrus and ovulation in breeder bitches with as a low dose as 0.6 microg/kg/day of cabergoline formulation marketed for use in women. Sixty-one pure breed bitches from various breeds were used in the study at their already determined periods of anestrus. Twenty-four dogs formed the control group, while 37 bitches were administered with two different doses of cabergoline (recommended dose group, n=10, 5 microg/kg/day and low dose group, n=27, 0.6 microg/kg/day). Induced estrus rates and mean treatment and proestrus durations of dogs in these two dose groups were compared. At the second phase of the study, the effects of 500 IU human chorionic gonadotropin (hCG) administered on days 1 and 3 of estrus induced by the low dose of cabergoline, on the duration of behavioral estrus, ovulation rates, pregnancy rates and the number of offspring were investigated. For this purpose, the dogs with signs of proestrus (22/27) following the treatment in the low dose group were assigned into two subgroups. Five hundred IU of hCG (Pregnyl, Organon, Turkey) was intramuscularly administered to eight of these dogs [low dose (hCG+) group] on days 1 and 3 of estrus. The remaining 14 dogs were not treated with hCG [low dose (hCG-) group]. An aqueous solution of cabergoline (Dostinex, Pharmacia, Italy) was orally administered until 2 day after the onset of proestrus or for a maximum of 42 days. Blood samples were taken daily from all treatment and 11 control bitches during the first five days of behavioral estrus to measure progesterone concentrations. In the recommended dose and low dose groups, estrus was induced between days 8-45 and 4-48 (mean: 23.63+/-14.33 and 24.41+/-14.31 days), in the ratio of 80.0 and 81.5%, respectively (p>0.05). In both dose groups, post-treatment interestrous intervals were significantly shorter than both those of the control group and their own pre-treatment interestrous intervals (p<0.05). Ovulation rates, pregnancy rates and mean number of offspring delivered by the dogs in the recommended dose, low dose (hCG-), low dose (hCG+) and control groups were found to be similar (p>0.05). However, the mean duration of behavioral estrus of the dogs in the low dose (hCG+) group was found to be significantly longer compared to dogs in all other groups (p<0.05). In both dose groups, no correlation could be found between the anestrus stages and treatment durations (p>0.05). Shortly, it has been concluded from the study that (1) normal and fertile estrus can be induced more economically in bitches during different stages of anestrus using as a low dose of 0.6 microg/kg of cabergoline formulation marketed for use in women, and that (2) hCG injections on days 1 and 3 of the estrus induced by this method has no positive effects on the ovulation rates, pregnancy rates and the number of offspring per pregnancy.     

Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus

Paraventricular (PVN) concentrations of neuropeptide Y (NPY), serotonin (5-HT) and dopamine (DA) in anorectic tumor-bearing (TB) rats were measured before and after tumor resection. At onset of anorexia in TB versus non-tumor bearing (NTB) Controls 5-HT increased from 12.19+/-0.49 pg/microg to 14.89+/-0.81 pg/microg ( P<0.05 ) while DA and NPY decreased from 7.34+/-0.42 pg/microg to 4.97+/-0.56 pg/microg and 23.47+/-4.27 pg/microg to 13.64+/-1.44 pg/microg, respectively ( P<0.05 ). After tumor resection, these neuromediators normalized when compared to sham-operated NTB rats. NTB pair-fed Controls were also studied. We conclude that the increased 5-HT and the decreased DA and NPY concentrations in PVN are associated with cancer anorexia and that the NPY food stimulatory effect is linked to serotoninergic and dopaminergic systems in hypothalamus.     

Effects of estrous cycle and sex on the expression of neuropeptide Y Y1 receptor in discrete hypothalamic and limbic nuclei of transgenic mice

In the present study we used a transgenic mouse model, carrying the neuropeptide Y (NPY) Y1 receptor gene promoter linked to the LacZ reporter gene (Y1R/LacZ mice) to test the hypothesis of its up-regulation by gonadal hormones. Y1 receptor gene expression was detected by means of histochemical procedures and quantitative image analysis in the paraventricular nucleus, arcuate nucleus, medial preoptic nucleus, ventromedial nucleus and bed nucleus of stria terminalis of two-month-old female mice at different stages of estrous cycle. Qualitative and quantitative analyses showed that Y1R/LacZ transgene expression was higher in the paraventricular, arcuate, and ventromedial nuclei of proestrus mice as compared to mice in the other stages of the estrous cycle. In addition, we performed a comparison with a group of sexually active males. In this comparison a significant difference (less in males) was observed between males and proestrus females in the same nuclei. In conclusion, these data indicate that fluctuations in circulating levels of gonadal hormones, depending by estrous cycle, are paralleled by changes in the expression of NPY Y1 receptor in the hypothalamic nuclei involved in the control of both energy balance and reproduction.     

Stage of the estrous cycle at the time of pregnant mare's serum gonadotropin injection affects pre-implantation embryo development in vitro in the mouse

The present study aims to analyze in the mouse the effect of the stage of the estrous cycle at the time of pregnant mare's serum gonadotropin (PMSG) injection on fertilization of ovulated cumulus-enclosed oocytes and later embryo development in vitro to the blastocyst stage. Quality of blastocysts was evaluated by staining and counting of total number of nuclei, mitotic index, percentage of apoptotic nuclei, and cell allocation to the inner cell mass (ICM) and trophectoderm (TE) lineage. Superovulation of hybrid (C57Bl/6JIco female x CBA/JIco male) female mice of 4-6 weeks of age was induced by a priming injection of PMSG at different stages of the estrous cycle followed after a 48-hr interval by human chrorionic gonadotropin. Our data indicate that injection of PMSG at the estrus phase gives the best outcome whereas injection of PMSG at the diestrus-1 or diestrus-2 phase provides the worst results. In fact, (1) total number of oocytes ovulated, number of ovulated oocytes enclosed by cumulus cells, and number of TE cells in day-5 blastocysts were significantly lower in diestrus-1 females than in estrus, diestrus-2 and proestrus mice; (2) percentage of day-5 blastocysts and total number of cells in day-5 blastocysts were lower in diestrus-1 and diestrus-2 females than in estrus and proestrus mice; and (3) percentage of apoptotic nuclei in day-5 blastocysts was lower in estrus mice than in diestrus-1, diestrus-2, or proestrus females. These data endorse previous studies suggesting that administration of gonadotropins in mice should be synchronized with the innate estrous cycle of females.     

Gender-related differences in myocardial inflammatory and contractile responses to major burn trauma

Gender-related differences in immune responses to hemorrhage and sepsis have been described. However, most trauma studies continue to limit experimental models to males to avoid the variable responses associated with hormonal fluctuation in proestrus/estrus females. In the present study, male and female (either diestrus or proestrus/estrus) Sprague-Dawley rats (250-325 g) were given a third-degree scald burn over 40% total body surface area and fluid resuscitated (4 ml/kg per %burn of lactated Ringer solution); sham burn males and diestrus as well as sham burn proestrus/estrus female rats were included to provide controls. Twenty-four hours postburn, hearts were either perfused to examine mechanical function (Langendorff, n = 8 to 9 hearts/group) or to prepare cardiomyocytes (collagenase digestion, n = 4 to 5 hearts/group). Left ventricular developed pressure and the positive and negative first derivative of left ventricular pressure responses to increases in preload were significantly lower in burned males compared with responses measured in either burned proestrus/estrus or burned diestrus females; burn trauma increased cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide to a lesser extent in proestrus/estrus females than levels secreted by either diestrus females or males. Similarly, myocytes from proestrus/estrus females accumulated significantly less sodium/calcium compared with values measured in males (P < 0.05). Our data confirm gender-related differences in myocardial function and myocardial inflammatory responses to burn injury.     

Regional effect of naltrexone in the nucleus of the solitary tract in blockade of NPY-induced feeding

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 microg in 0.3 microl) into the hindbrain region just prior to PVN NPY (0.5 microg, 0.3 microl) or artificial cerebrospinal fluid (0.3 microl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.     

Atrial supersensitivity to noradrenaline in stressed female rats

Stress can change the responses to catecholamines in many tissues. The aim of this study was to investigate the influence of the estrous cycle on the sensitivity of right atria to noradrenaline in female rats subjected to acute swimming stress. Female Wistar rats in proestrus, estrus, metestrus or diestrus were submitted to a 50 min-swimming session. Immediately after the exercise, the rats were killed and their right atria were mounted for isometric recording of the spontaneous beating rate. Concentration-effect curves to noradrenaline were obtained before and after the inhibition of neuronal uptake with phenoxybenzamine (10 microM) and of extraneuronal uptake with estradiol (5 microM). Acute swimming stress did not change the right atrial sensitivity to noradrenaline in rats in estrus, metestrus and diestrus. However, swimming stress produced supersensitivity to noradrenaline in proestrus (pD(2) control: 7.14 +/- 0.03 vs. pD(2) swimming: 7.55 +/- 0.04; p<0.05). This supersensitivity was still observed after uptake inhibition. When catecholamine uptake was inhibited, the concentration-effect curve to noradrenaline was shifted to the left 2.5-fold in the proestrus control group and 1.7-fold in the proestrus stress group (p<0.05). In conclusion, the estrous cycle influenced the acute stress-induced atrial supersensitivity to noradrenaline.     

Luteal regression in the normally cycling rat: apoptosis, monocyte chemoattractant protein-1, and inflammatory cell involvement

In hypophysectomized rats, prolactin induces regression of the corpora lutea. Luteal regression is accompanied by infiltration of monocytes/macrophages, declines in luteal mass and plasma progestins, and increased staining for monocyte chemoattractant protein-1 (MCP-1). We investigated whether similar events are induced during the estrous cycle, after the proestrous prolactin surge. Rats were killed on proestrus or on estrus, and one ovary was frozen for immunohistochemical detection of MCP-1, monocytes/macrophages (ED1-positive), and differentiated macrophages (ED2-positive) and for in situ detection of apoptotic nuclei. Corpora lutea of the current (proestrus) or preceding (estrus) cycle were dissected from the ovaries of additional rats and frozen for the same analyses and for determination of total protein content. In sections of whole ovaries, intensity and distribution of MCP-1 staining were increased in corpora lutea of multiple ages on estrus as compared to proestrus, as were numbers of differentiated macrophages and apoptotic nuclei per high-power field. Sections of isolated corpora lutea showed these increases on estrus, and the number of monocytes/macrophages per high-power field was also significantly increased. Accompanying these inflammatory/immune events, the corpora lutea on estrus showed decreased weight and total protein per corpus luteum, as compared to corpora lutea on proestrus. These changes are consistent with a proposed role for prolactin in the initiation of luteal apoptosis and of a sequence of inflammatory/immune events that accompany regression of the rat corpus luteum during the normal estrous cycle.     

Pain threshold variations in female rats as a function of the estrus Cycle

In this study, the response of female rats in different phases of the estrus cycle to nociceptive stimulation was evaluated using thermal (hot plate and tail immersion) and chemical (formalin) tests. In the hot plate test, the paw licking latency fell significantly (p < 0.05) in the metestrus and diestrus phases compared with the proestrus and estrus phases. The observations in the tail immersion test also followed the same pattern. The significant reductions in the paw licking and tail withdrawal latencies due to a lowered threshold denote an increase in pain sensitivity in the metestrus and diestrus phases. In the formalin test, the licking time fell significantly from the metestrus to the diestrus phase compared with the proestrus and estrus phases, the reduction in this test which was due to an increased threshold connotes a decrease in pain sensitivity. The results therefore seem test dependent. In conclusion, pain threshold in female rats depends on the estrus state. Keywords: Pain threshold, Variation, Estrus cycle.