Receptivity In Rats Research Articles

Pelvic neurectomy blocks oxytocin-facilitated sexual receptivity in rats

The effect of bilateral pelvic, hypogastric, or pudendal neurectomy on oxytocin-induced facilitation of lordosis behavior was examined in ovariectomized, estrogen, and progesterone primed female rats. Oxytocin-induced facilitation of lordosis behavior was significantly decreased following bilateral pelvic, or combined bilateral pelvic and hypogastric neurectomy. Hypogastric only or pudendal only neurectomy had no effect on the facilitation of lordosis behavior after systemic administration of oxytocin. These results suggest that the integrity of the pelvic nerve is necessary and sufficient to mediate the stimulatory effects of systemically administered oxytocin on receptivity.

Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat.

We investigated whether the transplant of Schwann cells prevents the physiological and morphological effects of monocular deprivation in the rat. On the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days, at the end of the critical period for the visual system development, we analyzed the functional properties of visual cortical neurons. Spontaneous discharge, orientation selectivity, and receptive field size of visual cortical neurons in transplanted animals were in the normal range. Transplantation of Schwann cells prevented the detrimental effects of monocular deprivation on ocular dominance and binocularity of cortical neurons. Visual acuity of the deprived eye estimated by visually evoked potentials was also normal. Schwann cells derived from adult animals were as effective as those derived from neonates. The effects of Schwann cells on monocular deprivation were dependent upon the number of cells present in the transplant so that 10(6) Schwann cells were sufficient to prevent the effect of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells. In rats transplanted with hybridoma cells producing an antibody that functionally blocks nerve growth factor (NGF), we found that the effect of cotransplanted Schwann cells on monocular deprivation was partly counteracted. We conclude that transplantation of Schwann cells prevents both functional and anatomical effects of monocular deprivation, presumably acting through the production of NGF. We propose that transplants of Schwann cells could be a promising technique for clinical applications.

Gd-DTPA MR detection of blood-brain barrier opening in rats after hyperosmotic shock.

Detection of blood-brain barrier (BBB) opening in neonates has required invasive methods not clinically applicable. We set out to develop a noninvasive approach to detect such opening. Wistar rats were studied using MRI with Gd-DTPA contrast before and after injection of hyperosmotic solutions known to produce barrier opening. Arabinose was given via right carotid artery to produce unilateral barrier opening; urea was given via tail vein to produce bilateral opening; controls received normal saline. Next, all animals received Gd-DTPA via tail vein. Animals receiving carotid hyperosmotic injections showed increased signal in the ipsilateral brain hemisphere; those receiving venous hyperosmotic injections showed increased signal bilaterally. Similar increases were not found prior to administration of hyperosmotic agent or in saline controls. In both cases, barrier opening was detectable using the relative partitioning of Gd-DTPA between intrabarrier and extrabarrier structures, even in the absence of a hemispheric control. We conclude that MRI with Gd-DTPA contrast allows noninvasive detection of BBB opening in the rat.

Progesterone facilitates lordosis, but not LH release, in estradiol pulse-primed male rats

Gonadectomized (GDX) male and female rats received repeated cycles of estradiol pulses, which prime animals of both sexes to display progesterone-facilitated lordosis. One, three and six treatment cycles of estradiol pulses followed by progesterone induced progressively higher luteinizing hormone (LH) surges in GDX females. Six treatment cycles of estradiol pulses alone (i.e., without subsequent progesterone treatment) induced a small but significant (∼4 ng/ml) increase in LH levels in GDX females. In contrast, GDX males never produced LH surges in response to estradiol pulses alone or estradiol pulses followed by progesterone, regardless of the number of hormone treatment cycles. Thus, female patterns of steroid-induced sexual receptivity and LH release are not inextricably linked, as steroid treatments sufficient for induction of lordosis do not stimulate LH secretion in adult male rats. These data also suggest that the neural system governing the LH surge might be more firmly sexually differentiated than that responsible for sexual receptivity in rats.

Electrophysiological Actions of Oxytocin on Hypothalamic Neurons in vitro: Neuropharmacological Characterization and Effects of Ovarian Steroids

Oxytocin (OT) neurotransmission in the brain has a facilitatory effect on sexual receptivity in rats. This effect of OT is dependent on priming by ovarian steroids, estrogen and progesterone. These steroids modulate OT binding in specific brain nuclei, including the ventrolateral portion of the ventromedial hypothalamic nucleus (vlVMN). In the present study, single-unit activity was recorded from the vlVMN in hypothalamic slices to characterize the electrophysiological actions of OT. To examine the effects of ovarian steroids on OT actions, we used brain slices prepared from ovariectomized rats either treated with estrogen or not, and some slices were treated with progesterone in vitro. OT had little modulatory action on neuronal responses to other agents, but affected the activity of large numbers of vlVMN units. Of those neurons affected, 94% responded with excitation. This predominant stimulatory action of OT is consistent with its lordosis-facilitating effect, because increases in the activity of VMN neurons are generally associated with the facilitation of lordosis. Pharmacological analyses with selective OT agonists and antagonists as well as structurally related peptides showed that the excitatory action of OT is mediated by OT receptors. Estradiol modulated several aspects of OT transmission. First, it increased neuronal responsiveness to OT, especially at the lowest concentration used (0.2 nM). In addition, it caused neuronal responses to OT to correlate significantly with responses to acetylcholine and norepinephrine, which also can act on the ventromedial hypothalamus to facilitate lordosis. Finally, estradiol enhanced the excitability of laterally projecting neurons, which have been implicated in lordosis. In estrogen-pretreated slices, addition of progesterone in vitro caused little further effect on responses of individual neurons to exogenous OT. Altogether, the present electrophysiological findings are consistent with the hypothesis that estrogen potentiates OT action by increasing functional OT receptors preferentially in lordosis-relevant neurons, thereby enabling OT to efficiently facilitate female reproductive behavior.

Surfactant and isoprenaline effect on eustachian tube opening in rats with acute otitis media

Purulent otitis media was induced in 12 middle ears of Sprague-Dawley rats by inoculation of pneumococci type 3. The pressure required to open the eustachian tube was recorded 4 days later and was found to be 3.05 ± 0.10 kPa (mean ± SEM), which was 1.08 ± 0.15 kPa lower than the mean value obtained in a control group of healthy rats ( P ⩽ .001). We also measured the effects of pulmonary surfactant instilled into the middle ear as well as isoprenaline injected intravenously. The presence of surfactant further reduced the pressure opening level by 0.72 ± 0.05 kPa; this reduction did not differ from that found in the control group ( P > .8). Isoprenaline reduced the pressure opening level in the control group by 0.20 ± 0.03 kPa ( P ⩽ .001), and no reduction was found in the rats with otitis media. Although the part played by surface tension-lowering factors in eustachian tube function is still uncertain, such factors apparently also exert an effect in the inflamed tube. However, isoprenaline, which is considered to act by the secretion of surface tension-lowering substances, did not facilitate opening of the eustachian tube in rats with acute otitis media.

Different responsiveness to progesterone for induction of pseudopregnancy between the first and the third estrous cycle after vaginal opening in rats.

Different responsiveness to progesterone for induction of pseudopregnancy between the first and the third estrous cycle after vaginal opening in rats.

Time Course of the Estradiol-Dependent Induction of Oxytocin Receptor Binding in the Ventromedial Hypothalamic Nucleus of the Rat*

Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

Medial preoptic area oxytocin and female sexual receptivity.

Intracerebroventricular (icv) administration of the nonapeptide oxytocin (OXT) increases sexual receptivity in female rats. The medial preoptic area (MPOA) appeared to be the most sensitive brain area to the facilitative effects of OXT. Bilateral infusions of 100 ng of OXT into the MPOA significantly elevated lordosis quotients in ovariectomized (OVX), estrogen-treated rats. This dose of OXT was ineffective when infused icv or into the ventromedial hypothalamus, mesencephalic central gray, or ventral tegmental area. A 500-ng dose of OXT significantly elevated lordosis responding when infused icv, corresponding with our previous findings. Mounting by males significantly increased immunoreactive levels of OXT and decreased the number of OXT immunostaining cells in the MPOA of sexually receptive rats pretreated with estrogen and progesterone. The MPOA is a primary site of the OXT facilitation of sexual receptivity where OXT may be released during mating.

GABA inhibits sexual behaviour in female rats

Ejaculation by male rats caused an abrupt and marked increase in the concentration of GABA in the cerebrospinal fluid and an equally abrupt and marked inhibition of sexual behaviour in female rats. The increase in the concentration of GABA in the cerebrospinal fluid and the inhibition of the behaviour was specifically mediated by the ejaculation of the male; sexual stimulation unaccompanied by ejaculation had no effect. The post-ejaculatory suppression of sexual receptivity in female rats was partially reversed by intracerebroventricular injection of the GABA antagonist bicuculline and the behaviour of receptive rats was inhibited by intracerebroventricular injection of the GABA agonist muscimol. Increasing the concentration of GABA in the ccrebrospinal fluid by i.p. injection of the GABA transminase inhibitor gamma-vinyl GABA caused an increase of the concentration of GABA in the cerebrospinal fluid and inhibited the display of sexual receptivity. It is suggested that GABA mediates physiologically relevant inhibition of sexual behaviour in female rats.

Sequelae of the osmotic blood-brain barrier opening in rats

Histopathological sequelae of the osmotic blood-brain barrier opening were studied in 69 adult Wistar rats sacrificed between 2 minutes and 6 days after infusion of 1.6 M mannitol into the unilateral internal carotid artery. The results were correlated with immunohistochemical localization of autologous albumin in the brain parenchyma on paraffin sections. Extravasation of serum albumin was evident in all rats, and the albumin immunoreactivity, commonly localized to the territories of the ipsilateral anterior, middle, and posterior cerebral arteries and contralateral anterior cerebral artery, showed maximum intensity in the rats sacrificed 30 minutes after infusion. The albumin immunoreactivity remained macroscopically visible in the brain parenchyma for 24 to 48 hours, and then gradually faded out. Serum extravasation was accompanied by widening of the perivascular space and focal edema, which largely subsided within 48 hours as the albumin immunoreactivity of the tissue diminished. Although no overt neurological sequelae were seen in the present experiment, minute but definite foci of infarction with focal accumulation of albumin were found in 23 (38%) of 61 rats surviving more than 30 minutes. In addition, ischemic neuronal death of delayed onset was encountered among neurons in the CA-1 region of the hippocampus, in the cerebellum, and in the thalamus in five (25%) of 20 rats sacrificed between Days 4 and 6. Thus, care should be exercised in the practice of this procedure.

Ovarian steroids and sexual interaction alter oxytocinergic content and distribution in the basal forebrain

The immunoreactive levels of oxytocin (OXY) were assessed by radioimmunoassay (RIA) and immunohistology after treatments with estradiol or estradiol and progesterone in ovariectomized rats that were mounted or not mounted by males. In micropunches from the medial preoptic area (MPOA) OXY immunoreactive levels increased significantly in estrogen-progesterone-treated receptive animals (mean lordosis quotient (LQ) = 82.9 ± 4.4) that were mounted by males over levels in estrogen-treated unreceptive animals (mean LQ = 2.3 ± 1.3). No other areas demonstrated significant changes in OXY levels across these treatments, although the paraventricular nucleus also had elevated OXY levels in receptive mounted females. In other animals, immunocytochemistry revealed that the number of oxytocinergic perikarya in the MPOA decreased in receptive animals (LQ= 86.7 ± 4.9) that were mounted. The number of oxytocinergic perikarya per 50 μm vibratome section in the lateral subcommissural nucleus was lower in all estrogen-treated groups than in oil vehicle-treated controls. We suggest that the combination of increasing immunoreactive levels of OXY in the MPOA with decreasing numbers of oxytocinergic perikarya indicates that preoptic OXY is moved out of cell bodies, in receptive rats that are mounted by males, to a state that is more accessible to the RIA.

The effect of naloxone on sexual behavior in female rats depends on the site of injection

Intraperitoneal injections of the opiate receptor antagonist naloxone (0.1, 1, 5 or 10 mg) had no effects on sexual behavior in ovariectomized female rats made either partially or fully receptive by injections of ovarian hormones. Intracerebroventricular (i.c.v.) injections of naloxone (10, 50 or 100 μg) had no effects on the behavior of partially receptive rats and in fully receptive rats an i.c.v. injection of a high dose of naloxone (100 μg) inhibited the behavior. Intrathecal (i.t.) injections of naloxone (50 or 100 μg) facilitated sexual behavior in partially receptive rats while i.t. injections of even very high doses of naloxone (500 μg) had no behavioral effects in fully receptive rats. Thus, the effects of naloxone on female sexual behavior depend on the site of injection.

Norepinephrine infusions into the medial preoptic area inhibit lordosis behavior

Neurotransmitters, including norepinephrine, have been implicated in the mediation of ovarian steroid induced lordosis behavior in ovariectomized rats. In this study we have found that norepinephrine (NE) infusions into the medial preoptic area (MPOA) reduced lordosis frequencies of estrogen-progesterone treated (0.5 μg estradiol benzoate for three days followed by 500 μg progesterone 4–5 hours before testing) receptive rats. Norepinephrine doses of 2 μg or more per animal infused into the MPOA significantly reduced lordosis levels within five minutes. Infusions of 10 and 20 μg doses of NE suppressed lordosis levels for 15 minutes after infusion. At the lowest inhibitory dose (2 μg/animal) simultaneous infusion of 5 μg/μl of the noradrenergic antagonist yohimbine, but not of phentolamine or propranolol, blocked the reduction in lordosis resulting from NE infusion. Preoptic infusions of epinephrine and clonidine were also effective in reducing lordosis quotients, while methoxamine, phenylephrine and isoproterenol did not alter receptivity. These findings are consistent with the conclusion that the direct effect of norepinephrine infusions into the MPOA is inhibition of lordosis responding. There is some evidence that this inhibitory influence is mediated by alpha 2-noradrenergic receptors.

Biochemical and radioautographic analysis of estrogen-inducible progestin receptors in female ferret brain and pituitary: Correlations with effects of progesterone on sexual behavior and gonadotropin-releasing hormone-stimulated secretion of luteinizing hormone

Cytosolic binding molecules for the synthetic progestin [3H]R5020, were isolated in vitro from several brain regions including preoptic area/anterior hypothalamus, mediobasal hypothalamus, medial amygdala and parietal cortex as well as the pituitary gland of ovohysterectomized female ferrets. Binding of [3H]R5020 to cortical cytosols was saturable, of high affinity (apparent dissociation constant of 2.0 nM), and was steroid specific. Pretreatment of ferrets with a Silastic capsule containing estradiol caused significant increments in the concentration of cytosolic R5020 binding sites in hypothalamus and pituitary gland, but not in the other brain regions studied. Brains of additional ovohysterectomized ferrets, which had been primed with estradiol prior to receiving an i.v. injection of [3H]R5020, were processed radioautographically. Intense labeling of cells was seen in the medial and lateral preoptic area, in the lateral hypothalamus, and in the ventromedial and arcuate nuclei of the hypothalamus. Radioautograms from the brains of additional ovohysterectomized ferrets given an i.v. injection of [3H]estradiol revealed labeled cells in all of the above regions, in addition to the basolateral portion of the septum, the bed nucleus of the stria terminalis, and in the anterior amygdaloid area as well as the medial and cortical nuclei of the amygdala. This distribution of neural progestin and estrogen binding sites resembles those previously reported for these steroids in the rat, guinea pig, hamster and macaque. Functional studies showed that acute s.c. implantation of a Silastic capsule containing progesterone to ovohysterectomized ferrets, which had been primed with a low dosage of estradiol, failed to augment their sexual receptivity in limited tests with stimulus males given 4 and 8 h after progesterone treatment. This result contrasts with the well-established facilitatory effect of progesterone on sexual receptivity in rat and guinea pig. Chronic exposure to a progesterone capsule caused significant reductions in sexual receptivity in ovohysterectomized ferrets which were implanted concurrently with a second Silastic capsule containing a high dosage of estradiol. Similar effects of progesterone have been reported in rat and guinea pig, but not in the rhesus monkey. Thus species differences in the ability of progesterone to facilitate or inhibit sexual receptivity are not readily explained by species differences in the neural distribution of estrogen-induced progestin receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for involvement of midbrain central gray in cholinergic mediation of female sexual receptivity in rats.

Experiments were designed to determine the role of the midbrain central gray (MCG) in facilitation of lordosis by cholinergic agonists. In Experiment 1, estradiol-treated female rats received microinjections of carbachol into the MCG and showed a dose-related behavioral facilitation to the agonist. In Experiment 2, MCG injections of oxotremorine (OXO), a selective muscarinic receptor agonist, yielded a dose-related facilitation; this was blocked by systemic pretreatment with scopolamine (SCOP), a muscarinic antagonist. In Experiment 3, MCG-lesion animals were injected unilaterally with OXO intraventricularly following contralateral injection of SCOP or vehicle. Females with MCG damage displayed significantly less facilitation than sham-lesion animals. Pretreatment with SCOP abolished lordosis facilitation in both groups. In addition, after treatment with estradiol and progesterone, sham-lesion females showed more receptivity than MCG-lesion females. Systemic injection of SCOP produced a significant decline in lordosis for both groups. On the basis of these data, it is suggested that the MCG plays an important role in the cholinergic mediation of female sexual receptivity.

Evidence for involvement of midbrain central gray in cholinergic mediation of female sexual receptivity in rats.

Experiments were designed to determine the role of the midbrain central gray (MCG) in facilitation of lordosis by cholinergic agonists. In Experiment 1, estradiol-treated female rats received microinjections of carbachol into the MCG and showed a dose-related behavioral facilitation to the agonist. In Experiment 2, MCG injections of oxotremorine (OXO), a selective muscarinic receptor agonist, yielded a dose-related facilitation; this was blocked by systemic pretreatment with scopolamine (SCOP), a muscarinic antagonist. In Experiment 3, MCG-lesion animals were injected unilaterally with OXO intraventricularly following contralateral injection of SCOP or vehicle. Females with MCG damage displayed significantly less facilitation than sham-lesion animals. Pretreatment with SCOP abolished lordosis facilitation in both groups. In addition, after treatment with estradiol and progesterone, sham-lesion females showed more receptivity than MCG-lesion females. Systemic injection of SCOP produced a significant decline in lordosis for both groups. On the basis of these data, it is suggested that the MCG plays an important role in the cholinergic mediation of female sexual receptivity.

Studies into the dual effects of serotonergic pharmacological agents on female sexual behaviour in the rat: Preliminary evidence that endogenous 5HT is stimulatory

The potential stimulatory and inhibitory effects on female sexual behaviour of five 5HT antagonists and five agents that increase 5HT activity, were noted in ovariectomised rats primed with various steroid regimes such that they were either “receptive” (LQ>50%) or “non-receptive” (LQ<50%). The 5HT antagonists cinanserin, mianserin, ketanserin and metergoline all inhibited behaviour in receptive rats. Methysergide and cinanserin stimulated behaviour in non-receptive rats. All the drugs which increased 5HTP activity, i.e., 5HTP, zimelidine, alaproclate, WY 26002 and quipazine stimulated sex behaviour in non-receptive rats. In rats that had been ovariectomised only, part of this effect was probably due to stimulation of adrenal progesterone, but a significant stimulatory effect could still be observed in ovariectomised-adrenalectomised rats. 5HT also had a significant inhibitory effect on receptive rats, and the other agonists showed a similar but non-significant tendency. In view of the fact that 4 out of 5 of the 5HT antagonists inhibited sexual behaviour, we hypothesise that 5HT has a stimulatory role in the control of female sexual behaviour. The possible mechanisms mediating the dual action of 5HT on female sexual behaviour are discussed.

Vasopressin alters female sexual behaviour by acting on the brain independently of alterations in blood pressure.

Subcutaneous (s.c.) administration of Arg-vasopressin (AVP) prolongs retention of a learned behaviour and elevates arterial blood pressure. Intracerebroventricular (i.c.v.) injection of a thousandfold lower dose of AVP than needed with s.c. injection produces the same behavioural effect, suggesting that AVP acts on the brain to control behaviour. However, as i.c.v. injection of AVP also elevates arterial blood pressure, it was suggested that AVP, and perhaps other peptides as well, influences behaviour indirectly by eliciting a peripheral response, for example blood pressure changes, rather than by acting directly on the brain. The suprachiasmatic nuclei (SCN) of the hypothalamus, a source of vasopressin production, inhibit sexual receptivity in oestradiol-17 beta-treated ovariectomized rats during the light phase of the daily lighting cycle, leading to speculation that vasopressin might inhibit sexual behaviour. Here we report that i.c.v. injections of AVP (1, 4 or 10 ng) inhibit sexual behaviour in receptive rats. This behavioural response is prevented by i.c.v. injection of an antiserum to AVP 30 min before AVP injection. Subcutaneous injection of a high dose of AVP (1 microgram) has no behavioural effect but elevates arterial blood pressure within 30 min of administration. Intracerebroventricular injection of a behaviourally effective dose of AVP (1 ng) has no effect on blood pressure. The results provide direct evidence that AVP can alter behaviour by an action on the brain and independently of its effect on blood pressure.

16. Carbonic anhydrase activity in the receptive rat uterus induced by 17-α-hydroxy progesterone and estradiol

16. Carbonic anhydrase activity in the receptive rat uterus induced by 17-α-hydroxy progesterone and estradiol