Effects of chronic estradiol benzoate treatment on amygdala kindled seizures in male rats

In the female species, effect of estrogens on seizure activity is well documented, but not much is known on the effect of this ubiquitous steroid hormone on the seizure activity of the male species. In the present study, fully kindled male rats were treated with various doses (10, 30 and 50 microg/kg, i.p.) of estradiol benzoate (EB) daily, and kindled seizure parameters such as seizure stage (SS), after discharge duration (ADD) and stage 5 duration (S(5)D) were recorded at various times (0.25, 3 h and every 24 h for 96 h) after the first of daily EB treatments. While the 10-microg/kg dose of EB failed to produce any significant effect, the 30-microg/kg dose induced a triphasic effect on seizure parameters. An initially rapid increment of ADD (after 0.25 h), followed by significant decrease of all parameters at 48 h and later a significant increase in S(5)D was observed 96 h after the first of daily EB treatments. The 50-microg/kg dose of EB produced almost a similar but less marked pattern of effects. Pre-treatment with a 3-mg/kg dose of tamoxifen citrate (TAM), not only blocked the EB (30 microg/kg) effects till 72 h but also reduced the ADD and S(5)D significantly after 0.25 h, when compared to its control group. While pre-treatment with the 10-mg/kg dose of TAM only blocked the inhibitory effects of EB 48 h after the first of daily EB treatments. Administration of the latter dose of TAM alone induced a profile similar to EB treatment. These results may suggest that in male rats, estradiol treatment can both potentiate and attenuate kindled seizure parameters in a time dependent manner, and the stimulatory effects can not be blocked by TAM pre-treatment.     

The acute effects of estradiol benzoate on amygdala-kindled seizures in male rats

Using amygdaloid-kindling model of epilepsy, effects of acute estradiol treatment on seizure parameters were investigated in male rats. Fully kindled male rats were treated with various doses of estradiol benzoate (EB, 10, 30 and 50 microg/kg, i.p.) and kindling parameters such as seizure stage (SS), afterdischarge duration (ADD) and stage 5 duration (S5D) were elicited at various times (0.25, 1.5, 3 h and every 24 h for 96 h) post-drug administration. While the 10-microg/kg dose of EB failed to change seizure parameters, administration of the 30- and 50-microg/kg doses caused significant prolongation of ADD and S5D (was not changed significantly by the latter dose) at various time intervals post-drug administration. Pretreatment with the 3 mg/kg dose of tamoxifen citrate (TAM) inhibited the EB (30 microg/kg) effect, while pretreatment with the 10-mg/kg dose produced significant prolongation of ADD and S5D. These results suggest that in male amygdaloid kindled rats, acute estradiol treatment leads to an intensification of seizure that is manifested by increases in ADD and S5D. As the effect is evident 0.25 h post-EB administration and duel action of TAM in opposing the EB effect at low doses and potentiating it at the higher doses, the possibility of a genomic effect may be ruled out. The variable effects of TAM might be explained by its partial agonistic property on estrogen receptors     

Estradiol and progesterone influence a serotonin mediated behavioral syndrome (myoclonus) in female guinea pigs: Comparison with steroid effects on reproductive behavior

L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus was used as a behavioral index of central serotonergic activity. Estradiol benzoate (EB) and progesterone (P) influenced the induction of myoclonus by L-5-HTP. When L-5-HTP was injected 46 h after EB, myoclonus was enhanced. P blocked this effect on EB when 100 or 125 mg/kg L-5-HTP (but not 80 mg/kg) was given 6 h after P in EB-primed animals. When L-5-HTP was given 3 or 11-15 h after P in EB-primed animals, there was no inhibitory effect of P on myoclonus. In fact, at the lowest dose (80 mg/kg), L-5-HTP increased myoclonus when given 3 h after P in EB-primed animals. The inhibitory effects of P in EB-primed females on myoclonus were temporally correlated with the display of lordosis, suggesting that the neural progestin receptor mechanisms that have been proposed to mediate P effects on lordosis are also involved in the inhibitory effects of P on myoclonus.     

The role of delta-opioid receptors in estrogen facilitation of lordosis behavior

The present study investigated the role of delta-opioid receptors (ORs) in estrogen facilitation of female rat reproductive behavior (lordosis). Infusion of 2 microg of the selective delta-OR agonist [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE), into the third ventricle facilitated lordosis behavior in ovariectomized (OVX) rats injected with estrogen (E) 48 and 24 h before behavioral testing. Pretreatment with the selective delta-OR antagonist naltrindole (NTDL) blocked DPDPE effects on lordosis behavior. Ventricular infusion of NTDL (40 microg) also suppressed lordosis behavior in fully receptive OVX rats primed with both E and progesterone (P). In addition, NTDL blocked lordosis behavior when infused into the ventromedial nucleus of the hypothalamus (VMH) but not into the medial preoptic area (mPOA). Site-specific infusion of DPDPE into the VMH had dose-dependent, dual effects on lordosis behavior. While a very low dose of DPDPE (0.01 microg) facilitated lordosis behavior, a higher dose (1.0 microg) inhibited receptivity in OVX rats primed with E and a low dose (50 microg) of P. We used 3H-DPDPE to measure the density of delta-ORs in OVX rats treated with vehicle or with E by receptor autoradiography. E treatment did not have any effect on the density of DPDPE binding sites in the VMH, mPOA, medial amygdala, or caudate putamen. The behavioral effects of the ligands used in this study suggest that activation of delta-OR in the VMH by endogenous opioids facilitates estrogen-dependent lordosis behavior.     

Effect of estrogen on the lordosis-inhibiting action of ketanserin and SB 206553

The effects of the 5-HT(2A/2C) receptor antagonist, ketanserin, and the 5-HT(2C) receptor antagonist, SB 206553, on lordosis behavior were investigated in ovariectomized rats hormonally primed with estradiol benzoate (EB) (0.5 or 25 microg) and progesterone (500 microg). Both ketanserin and SB 206553 inhibited lordosis behavior after infusion into the ventromedial nucleus of the hypothalamus (VMN), but ketanserin was slightly more effective than the 5-HT(2C) receptor antagonist. Either drug was more effective in rats primed with 0.5 microg EB than in rats hormonally primed with 25 microg EB. These findings support the suggestion that estrogen may enhance functioning of the 5-HT(2) receptor family and thereby protect against the 5-HT(2) receptor antagonists. These data are consistent with prior suggestions that estrogen modulates functioning of 5-HT(2) receptors within the VMN and that 5-HT(2) receptors play a facilitatory role in the modulation of female rat lordosis behavior.     

Monoamines, estrogen and female sexual behavior in the golden hamster

In the golden hamster drugs which inhibit monoaminergic function (including p-chlorophenylalanine (PCPA), methysergide and a-methyl-p-tyrosine (a-MPT) facilitated lordosis in ovariectomized female hamsters as a function of the duration of estradiol benzoate (EB) priming. a-MPT (200 mg/kg), methysergide (6 mg/animal) or PCPA (150 or 360 mg/kg) potentiated lordosis if 6 days of EB priming preceded drug treatment. However, if female hamsters were primed with EB for only 2 days, a-MPT and methysergide were ineffective. PCPA (360 mg/kg) was less effective after 2 days of EB than after 6 days of EB priming. alpha-MPT produced a three-fold elevation in progesterone levels in ovariectomized females but methysergide and PCPA did not influence serum progesterone. PCPA (360 mg/kg) facilitated lordosis in adrenalectomized, ovariectomized females, eliminating the possibility that adrenal progesterone is essential for the behavioral effects of the drug. Luteinizing hormone-releasing hormone levels in the preoptic/anterior hypothalamic area and the medial basal hypothalamus were also not significantly altered at 1 h after PCPA injection. Pimozide (1.5 mg/kg) and pimozide (1.5 mg/kg) and amphetamine (2.5 mg/kg) did not potentiate lordosis in ovariectomized hamsters after either 2 or 6 days of EB priming. Pargyline, a monoamine oxidase inhibitor, inhibited female sexual behavior in females in estrogen alone-induced estrus. Lordosis in the female rat is more readily elicited both by drugs and estrogen. It is proposed with regard to female sexual behavior that species differences in estrogen sensitivity may underlie apparent differences in drug sensitivity.     

Noradrenergic transmission and female sexual behavior of guinea pigs

Treatment with the dopamine beta-hydroxylase (DBH) inhibitor U-14,624 (50, 100, or 150 mg/kg) blocked the induction of lordosis behavior be estradiol benzoate (EB) and progesterone (P) in ovariectomized guinea pigs. After treatment with U-14,624 (100 mg/kg), norepinephrine (NE) content of medial basal hypothalamus, preoptic area and cortex was reduced (by 55%) and dopamine (DA) content of medial basal hypothalamus was increased (by 155%) during the period when females treated with EB and P normally display lordosis. Treatment with the NE receptor stimulator clonidine (1.0 mg/kg) restored lordosis behavior in females treated with EB, P, and U-14,624 (100 mg/kg), but the putative DA and serotonin (5-HT) receptor blockers pimozide (1.0 mg/kg) and methysergide (20.0 mg/kg) were ineffective in this respect. Thus, inhibition of lordosis after treatment with U-14,624 appeared to be attributable primarily to a reduction in NE neurotransmission, rather than to increase in DA or 5-HT activity. Because clonidine induced lordosis in females treated with EB, P, and U-14,624, it seemed unlikely that the facilitatory effects of clonidine on lordosis were mediated by activation of presynaptic alpha-adrenergic receptors (i.e. inhibitory NE autoreceptors) rather than by postsynaptic alpha-receptors. In addition, pretreatment with the postsynaptic alpha-adrenergic antagonist phenoxybenzamine (20.0 mg/kg) blocked the facilitation of lordosis by clonidine (1.0 mg/kg) in females primed with EB alone and with EB plus P. Thus, the facilitatory effects of clonidine on lordosis appear to be mediated by activation of postsynaptic alpha-adrenergic (i.e. NE) receptors. The results of this study provide further evidence that NE neurotransmission facilitates the expression of female sexual behavior in guinea pigs.     

Suppressive effect of neonatal treatment with a phytoestrogen, coumestrol, on lordosis and estrous cycle in female rats

The neural control systems for the ovulatory cycle and lordosis behavior are sexually differentiated by estrogen during the perinatal period in rats. In the present study, the effects of a single neonatal injection with the phytoestrogen, coumestrol, on female reproductive functions were investigated. Female rats were injected subcutaneously with 1 or 3mg coumestrol (CM1, CM3), 1mg genistein (GS1), 1mg estradiol (E2), or oil at day 5 after birth (birth day=day 1) and an estrous cycle check and lordosis behavior test were performed. As a result, vaginal opening was advanced in CM1-, CM3- or E2-treated females. A vaginal smear check indicated that oil- or GS1-treated females showed a constant 4- or 5-day estrous cycle, whereas CM1-, CM3- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovary weights in the CM1-, CM3- or E2-treated groups were lower than those in the oil- and GS1-treated groups and no corpora lutea were found in any rats of these three groups, except for two E2-treated rats. Behavioral tests were carried out after implantation of E2-tubes. All rats in the CM1-, GS1-treated groups showed a high lordosis quotient (LQ), being comparable to that in the oil-treated females. On the other hand, LQs in the CM3, E2 or male groups were lower than that in the control female group. These results suggest that a single neonatal injection of 3 mg coumestrol was effective in suppressing the functions of ovulation-inducing mechanisms and the induction of lordosis, but 1mg coumestrol was effective in only the estrous cycle of female rats.     

Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT,and of mild restraint on lordosis behavior

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.     

Ibotenic acid-induced lesions of the medial preoptic area/anterior hypothalamus enhance the display of progesterone-facilitated lordosis in male rats

Electrical lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) have been reported to enhance the display of steroid-induced lordosis in castrated male rats. This study employed the cell body-specific neurotoxin, ibotenic acid, to ascertain whether neurons originating in this region (as opposed to axons of passage) tonically inhibit steroid-induced lordosis in adult male rats. Castrated, adult Long-Evans males received bilateral electrical lesions or injections of ibotenic acid or vehicle aimed at the MPOA/AH. Following administration of estradiol benzoate (EB) and progesterone, lordosis quotients (LQs) and lordosis ratings (LRs) were significantly higher in groups of rats with electrical lesions (LQ= 62.2 ± 15.1;LR= 1.22 ± 0.34) and ibotenic acid-induced lesions (LQ = 58.1 ± 12.2;LR= 0.99 ± 0.24) than in the control group (LQ= 12.8 ± 7.3;LR= 0.22 ± 0.13). To determine whether this enhancement of receptive behavior in MPOA/AH-lesioned males was an effect on estradiol-induced, as compared to progesterone-facilitated lordosis, groups of castrated rats in a second experiment received bilateral injections of ibotenic acid or vehicle aimed at the MPOA/AH and were tested for lordosis after administration of EB alone and again after injection of progesterone. Following treatment with EB alone, rats with ibotenic acid-induced MPOA/AH lesions tended to be slightly less receptive than control animals. However, following injections of progesterone, LQs and LRs were higher in the MPOA/AH-lesioned group than in the control animals, as had been observed in the first experiment. These data are consistent with the hypothesis that cell bodies, rather than axons of passage, originating in the MPOA/AH exert tonic inhibitory control over the display of progesterone-facilitated lordosis in adult male rats.     

Effects of septal lesions and testosterone on lordosis behavior and luteinizing hormone release in female rats

The increased behavioral sensitivity to estrogen following a septal lesion in female rats has previously been found to be blocked by chronic treatment with testosterone propionate (TP) following the lesion. The effects of this chronic treatment on the ability of progesterone (P) to facilitate the secretion of luteinizing hormone (LH) in the spayed septal lesioned rat primed with estradiol benzoate (EB) was tested in the present study. EB was injected and followed 72 hr later with an injection of P. Blood samples for measurement of plasma LH were taken at 1700 hr, 29 and 53 hr after EB and 5 hr after P injection. Although there was no effect of the lesion, TP treatment significantly inhibited LH values after P administration. In a second experiment, spayed septal lesioned or sham operated rats were given either 0.0, 0.5 or 2.0 μg EB followed by 0.5 mg P just 24 hr later. The display of lordosis behavior, tested 4–6 hr after P injection, was significantly greater in septal lesioned than in sham operated rats following priming injections of 0.5 or 2.0 μ EB. This indicates that septal destruction significantly shortened the duration required for estrogen to prepare neural mechanisms for the effect of progesterone on lordosis behavior. Following a similar steroid regime, no differences were found between lesioned and sham operated rats in plasma LH levels in blood samples taken 5 hr after EB or 5 and 29 hr after P injection.     

Alterations by estrogen and hypothyroidism in the effects of septal lesions on lordosis behavior of male rats

Earlier experiments indicated that chronic exposure to estradiol benzoate (EB) following septal lesions can increase the subsequent levels of female sexual behavior in male rats tested several months later following priming doses of EB. However, the present study demonstrates that a single injection of a large dose of EB (50 μg) two days after septal destruction did not modify subsequent responsiveness to EB priming in male rats relative to sham operated controls. Yet male rats given 10 daily injections of 5.0 μg EB/day immediately following a septal lesion were more responsive to EB than oil treated controls when tested later for lordosis behavior. Therefore, the capacity for EB to alter the behavioral effects of septal lesions on lordosis behavior in male rats is related to both chronic administration and a period of susceptibility to some action of EB during the immediate post-lesion period. In two additional experiments, chronic hypothyroidism induced by propylthiouracil or thyroidectomy was also found to modify the effects of septal lesions on female sexual behavior of male rats. These latter results indicate that EB is not unique in its capacity to alter the behavioral effects of septal lesions in male rats, and are consistent with the view that both EB and hypothyroidism may interact with some dynamic process associated with recovery from brain lesions.     

ERalpha, but not ERbeta, mediates the expression of sexual behavior in the female rat

Estrogen has well known effects on sexual behavior, however the role of the estrogen receptors (ER) alpha and beta on sexual behavior remains to be fully determined. This study investigated the individual and co-operative involvement of ERalpha and beta on sexual behaviors in the adult female rat. Subtype selective ER agonists, propyl-pyrazole triol (PPT; ERalpha agonist) and diarylpropionitrile (DPN; ERbeta agonist) were utilized to examine each receptor subtype's contribution, individual and co-operative, for both receptive (lordosis) and proceptive (hopping/darting, 'ear wiggling') female sexual behaviors. Ovariectomized female rats received subcutaneous injections of either: sesame oil (OIL), dimethylsulfoxide (DMSO), estradiol benzoate (EB; 10 microg/0.1 ml OIL), one of three doses of the ERalpha agonist PPT (1.25mg, 2.5mg or 5.0mg/0.1 ml DMSO), one of three doses of the ERbeta agonist DPN (1.25mg, 2.5mg or 5.0mg/0.1 ml DMSO) or a combination dose of PPT and DPN (2.5mg PPT+2.5mg DPN/0.1 ml DMSO) for two consecutive days, 48 and 24h prior to testing followed by a progesterone injection (500 microg/0.1 ml OIL) 4h prior to testing in order to elicit sexual behavior. The ERalpha agonist PPT, but not the ERbeta agonist DPN, elicited both proceptive and receptive behavior. PPT at doses of 2.5 and 5.0mg significantly elicited lordosis and proceptive behavior ('ear wiggling', hopping and darting). Intriguingly, the administration of both agonists together at the 2.5mg dose resulted in reduced levels of proceptivity and receptivity, suggesting that ERbeta modulates ERalpha's ability to elicit receptive and proceptive sexual behavior.     

Effects of tetrabenazine on lordosis behaviour and on brain monoamines in the female rat

Summary The time course of action of tetrabenazine (TBZ), 2 and 10 mg/kg i.p., on lordosis behaviour and on brain monoamines in ovariectomized estrogen pretreated female rats, was studied. The administration of TBZ (2 mg/kg) produced a decrease in brain DA and an increase in the number of lordosis, whereas 10 mg/kg of TBZ resulted in the same increase in lordosis behaviour as 2 mg/kg and a significant decrease in NA, DA and 5-HT. The results suggest that a decrease in brain monoamine levels, especially DA, facilitates lordosis behaviour in estrogen-TBZ treated female rats.     

Comparative Effects of Estradiol Benzoate, the Antiestrogen Clomiphene Citrate, and the Progestin Medroxyprogesterone Acetate on Kainic Acid-Induced Seizures in Male and Female Rats

We have investigated the comparative effects of estradiol benzoate (EB), the antiestrogen clomiphene citrate (CC), and the progestin medroxyprogesterone acetate (MPA) on seizures induced by systemic injection of kainic acid (15 mg/kg i.p.) in male and female rats. Subcutaneous administration for 10 days of EB (10 micrograms/kg) or high doses of CC (50 mg/kg) significantly potentiated kainate-induced seizures, with this effect being more pronounced in male animals. Doses of 2.5 mg/kg of CC potentiated kainate-induced seizures in male rats but were ineffective in female rats. Low doses of CC (0.5 mg/kg) exhibited a mild anticonvulsant effect in both sexes. Repeated administration of MPA (2.5 mg/kg) partially protected female animals against kainate-induced seizures; in male animals, MPA induced a 30% increase in the seizure severity score, although the difference from the score of control male rats was not significant. These data suggest that sex steroids influence kainate-induced seizures in a sex-dependent manner and that the effects of the antiestrogen CC are dose dependent. This should be taken into account in view of a possible use of CC and MPA in hormonal therapy for seizure disorders.     

Oxytocin facilitates the sexual receptivity of estrogen-treated female rats

Oxytocin (OXY) and arginine-vasopressin (AVP) are widely distributed within the brain and have a number of behavioral effects resulting from central administration. We have previously found that central OXY administration accelerated the onset of maternal behavior in ovariectomized (OVXed) estrogen-treated nulliparous rats. We now report that intracerebroventricular (ICV) injections of OXY enhance lordosis behavior in OVXed estrogen-treated rats. After treatment with 0.15, 0.20, or 0.25 micrograms EB IM for three days, OXY (800 ng) infusion ICV on the fourth day produced a significant increase in lordosis behavior between 20 and 90 minutes after administration. Doses of OXY between 0.8 and 5 micrograms injected ICV significantly increased lordosis behavior in animals pretreated with 0.5 micrograms EB for three days. In other OVXed rats treated with 0.5 micrograms EB for three days, ICV injections of 1 micrograms OXY or an equimolar dose of AVP significantly increased lordosis while equimolar doses of ACTH1-10, ACTH4-10, arginine-vasotocin, GnRH and alpha-MSH did not significantly increase lordosis behavior over saline vehicle levels. ACTH1-24 significantly lowered lordosis quotients. We have concluded from these data that central administration of OXY (and possibly AVP) enhance female sexual receptivity. This effect is estrogen dependent, dose related and under our test conditions, specific to OXY and AVP.     

Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice

Aggressive behaviour of gonadally intact male mice is increased by estrogen receptor (ER)-beta gene disruption, whereas sexual behaviour remains unchanged. The elevated aggression levels following ER-beta gene disruption is pronounced during repeated aggression tests in young animals and the first aggression test in adults. In the present study, the roles of ER-beta activation in the regulation of aggressive and sexual behaviour were investigated in gonadectomized ER-beta knockout (betaERKO) and wild-type (WT) male mice treated with various doses of estrogen. Overall, estradiol benzoate (EB) treatment induced higher levels of aggression in betaERKO mice than in WT mice. In WT mice, the levels of aggression induced by EB were highest in the lowest-dose (2.5 microg/day) group and gradually decreased in higher-dosage groups. On the other hand, equally high levels of aggressive behaviour were induced by all three doses of EB in betaERKO mice. A marked genotype difference in dose responses is inferred, such that the ER-alpha-mediated facilitatory action of estrogen is more pronounced at lower and physiological doses and the ER-beta-mediated inhibitory action is only unveiled at higher doses of estrogen. In contrast to aggression, the levels of sexual behaviour induced by EB were not different between betaERKO and WT at either dose of EB (2.5 and 12.5 microg/day) examined. These findings support the notion that ER-beta activation may exert an attenuating action on male aggression induced by estrogen through ER-alpha-mediated brain mechanisms, whereas its effect on male sexual behaviour is relatively small.     

Acute effects of sex steroids on lordosis behaviour of the female rat

In the present series of experiments, dose-response and time-response relationships between single injections of sex steroids and the display of lordosis behaviour in the female rat, were investigated. When injected 48 h prior to testing, increasing doses of estradiol benzoate (EB) or testosterone propionate (TP) resulted in increasing levels of lordosis behaviour. TP was much less effective than EB in facilitating lordosis behaviour in the female rat. The optimum time interval between hormonal treatment and testing was 48-72 h for TP, but 48 h for EB. Single injections of dihydrotestosterone propionate (DHTP), also injected 48 h prior to testing, inhibited lordosis behaviour in EB-primed female rats. DHTP-inhibition of lordosis behaviour in EB-primed female rats was most effective when given prior to and least effective when given after EB-treatment. Progesterone, injected 4 h prior to testing, facilitated lordosis in EB-, TP- or EB + DHTP-treated female rats.     

The role of the estrogen receptor α in the medial preoptic area in sexual incentive motivation, proceptivity and receptivity, anxiety, and wheel running in female rats

Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor α (ERα) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they were tested in the light/dark choice procedure, and after another 2 weeks they were subjected to a test in a brightly lit open field. Finally, the females were given free access to a running wheel for 88h. The females were treated with estradiol benzoate (EB), 18 or 1.5μg/kg, in randomized order 52h before each test except the running wheel. In that experiment, they were given EB 48h after introduction into the wheel cage. They were given progesterone, 1mg/rat, about 4h before all tests, except the running wheel. The shRNA reduced the number of ERα with 83%. Females with few ERα in the MPOA showed increased lordosis quotient after the 1.5μg/kg dose of EB. There was no effect on proceptive behaviors or on rejections. When given the 18μg/kg EB dose, there was no difference between females with few preoptic ERα and controls. In the test for sexual incentive motivation, females with few preoptic ERα approached the castrated male incentive more than controls, regardless of EB dose. They also moved a shorter distance. In the light/dark choice test as well as in the open field, females with few ERα in the MPOA showed signs of reduced fear/anxiety, since they spent more time in the light part of the dark/light box and in the center of the open field. Finally, the data from the running wheel showed that females with few preoptic ERα failed to show enhanced activity after treatment with EB. These data show that the preoptic ERα inhibits lordosis in females with an intermediate level of receptivity while it fails to do so in fully receptive females. The ERα in the MPOA seems to be necessary for selective approach to a sexual incentive. Finally, activation of this receptor appears to have anxiogenic effects in the procedures employed here. A hypothesis for how all these actions of the preoptic ERα contributes to efficient reproductive behavior is outlined.