Receptivity In Female Hamsters Research Articles

Protein Synthesis in the Medial Preoptic Area Is Important for the Mating-Induced Decrease in Estrus Duration in Hamsters

Sexual receptivity in female hamsters potentially lasts for about 16 h. However, vaginal cervical stimulation (VCS) from a male during mating eventually reduces receptivity and can shorten the duration of behavioral estrus. The process by which this change in response to the male takes place is unknown. Recently, detection of the Fos protein has indicated that the medial preoptic area (POA) is one of the brain regions particularly responsive to VCS. Additionally, the POA may have an inhibitory effect on sexual receptivity. To determine if protein synthesis in the POA is required to initiate the VCS-induced decrease in estrus duration, a protein synthesis inhibitor (anisomycin, 0.50 μg) or a control substance (cholesterol) was applied bilaterally to the POA of steroid-primed ovariectomized female hamsters. Females were tested with a sexually active male at five time points following the initial test for sexual receptivity (hour 1, 2, 6, 12, and 24). Half of the females tested were allowed to receive VCS from a male, while half were fitted with vaginal masks to prevent penile intromission. Each group receiving VCS showed a significant decrease in lordosis duration evident between hour 2 and hour 6, except the group which received anisomycin in the POA. In this respect the POA anisomycin group was similar to animals which did not receive VCS. Hamsters with vaginal masks and the anisomycin/POA animals allowed to receive VCS exhibited their first decrease in lordosis duration between hour 6 and hour 12. These results indicate that protein synthesis is important for VCS-induced decrease in estrus duration in the POA.

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH 2) 5[Tyr(Me) 2Thr 4,Tyr-NH 29] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Bicuculline infused into the hamster ventral tegmentum inhibits, while sodium valproate facilitates, sexual receptivity

Progesterone's (P) actions on both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) are essential for sexual receptivity in female hamsters. Evidence suggests that progesterone's actions in the hamster VMH may be genomic while those in the VTA may be mediated nongenomically, via GABA A. Ovariectomized female hamsters were bilaterally implanted with cannulae aimed toward the VTA. One week after surgery, animals were SC injected with 10 μg estradiol benzoate (EB) and 40 h later with 200 or 500 μg P. At hour 43.5, 50 ng bicuculline, a GABA A antagonist, was infused into each available cannula. Control animals received 0.5 μl sterile saline vehicle, or no infusion. At hour 44, animals were tested for sexual receptivity in an observation arena with a sexually experienced male. Histology revealed that only animals with bicuculline infused into the VTA had reduced lordosis durations compared to controls. Other animals, primed with EB and 200 μg progesterone, showed a facilitation of sexual receptivity after infusion into the VTA of 50 μg sodium valproate, a GABA A transaminase inhibitor. These results suggest that GABA A plays a necessary role in the mechanism of progesterone's actions on sexual receptivity in hamster VTA.

3α-OH-DHP and 5α-THDOC implants to the ventral tegmental area facilitate sexual receptivity in hamsters after progesterone priming to the ventral medial hypothalamus

Progesterone (P) stimulation to both the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) is necessary to facilitate sexual receptivity in female hamsters, despite the sparse population of estrogen-induced P receptors found in the VTA. Instead, P may act at neuronal membranes in the VTA. These P effects may be mediated by actions on the γ-aminobutyric acid A-(GABA A)-benzodiazepine receptor complex (GBR). Many progestin metabolites have a greater effect in vitro on benzodiazepine binding and Cl - flux than P. If P's actions are due to metabolism to a progestin more potent at the GBR, then applying one of those progestin metabolites directly to the VTA should facilitate receptivity, if coupled with P to the VMH. To test this hypothesis three P metabolites, in decreasing order of activity at cortical synaptosome GBR, were tested: 5α-pregnan-3α-ol-20-one (3α-OH-DHP), 5α-pregnan-3γ,21-diol-20-one (5α-THDOC) and 5β-pregnan-3α,21-diol-20-one (5β-THDOC). Ovariectomized hamsters were implanted with chronic cannulae, one aimed above the VMH and the other over the contralateral VTA. Animals were estrogen-primed and tested for sexual receptivity 4 h after a P containing insert was applied to the VMH and a metabolite containing insert was applied to the VTA. The following week the contents of the tubes were reversed; on the third week P was applied to both sites. Facilitation of receptivity occurred only when P was applied to the VMH and either P or a metabolite was applied to the VTA. The reversed treatment was not effective. The progestin metabolites in order o f behavioral effectiveness were:3α-OH-DHP= 5α-THDOC> 5β-THDOC. This behavioral rank order is consistent with an action at the GBR.

Muscimol facilitates sexual receptivity in hamsters when infused into the ventral tegmentum

Progestogenic stimulation of both the ventral medial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) within the midbrain is critical for normal receptivity in female hamsters. However, few estrogen-induced progestin receptors have been found in the midbrain. In addition, recent evidence suggests that progestin's action in the VTA is mediated nongenomically at the membrane. The present experiment investigated the possible role of GABAA receptors in mediating the effects of progesterone in this brain region. Ovariectomized female hamsters were bilaterally implanted with chronic cannulae aimed toward the ventral mesencephalon. Five days after surgery, animals were injected with 10 μg estradiol benzoate SC. Forty hours later, the same animals were injected with either 25 or 100 μg progesterone and at hour 43.5, 50 ng muscimol was infused in 0.5 μl. Control animals received 0.5 μl vehicle, sterile saline, or no infusion. At hour 44, animals were tested for sexual receptivity by placing them in an observation arena with a sexually experienced male for 10 min, during which lordosis duration was recorded. The following week, the same regimen was given with the alternate dose of progesterone. Histology revealed that only those animals that were infused with muscimol into the VTA had total lordosis durations that were significantly longer than the controls. Implants that missed the ventral tegmental area were much less effective. These results indicate that GABA might play a facilitatory role in enhancing the efficacy of threshold doses of progesterone. Whether this interaction is due to a direct effect of progestins on the GABAA receptor complex awaits further study.

Ventral tegmental lesions impair sexual receptivity in female hamsters

The ventral mesencephalon appears to be one of the sites of progesterone action in the control of sexual receptivity in female hamsters. The behavioral response to systemic progesterone was assessed in female hamsters following electrolytic lesions of portions of the ventral mesencephalon. Adult female hamsters were ovariectomized and pretested for sexual receptivity, then were given bilateral lesions aimed at the region of the ventral mesencephalon where progesterone implants have been shown to facilitate receptivity. Lesions were produced by stereotaxically lowering an electrode and applying anodal direct current of 1–2 mA for 5–20 seconds. One week later the hamsters were injected with estrogen followed 44 h later by progesterone. They were then tested for sexual receptivity. After this test, their brains were removed and histologically prepared. Lesion location was determined and lesion size was quantified with a digitizing pad. Lesions which were centered in and destroyed much of the ventral tegmental area produced the greatest lordosis impairments. Mesencephalic lesions which did not bilaterally damage the ventral tegmental area had little effect. These results support the hypothesis that the ventral mesencephalon. particularly the ventral tegmental area, is an important site for the facilitative action of progesterone on sexual receptivity in estrogen-primed female hamsters.

Intravenous administration of progesterone and the onset of receptivity in female hamsters

Progesterone-facilitated receptivity is believed to be a genomically mediated event. However, in contrast to estrogen, progesterone's effects occur rapidly. This experiment was designed to examine the temporal onset of receptivity in hamsters following intravenous (IV) administration of progesterone. Ovariectomized female hamsters were tested for their responsiveness to 10 μg estradiol benzoate (EB) plus 0, 50, or 200 μg progesterone, administered subcutaneously (SC). The hamsters were tested for sexual receptivity at 0.5, 1, 1.5, 2, 3 and 4 h. Three days later they were fitted with jugular catheters. Two days after catheter implantation they received 10 μg EB SC; 48 h later they were tested for receptivity and then received an IV injection of 0, 50, or 200 μg progesterone in 0.2 ml propylene glycol. Following the IV P injection the animals were again tested at 0.5, 1, 1.5, 2, 3 and 4 h. Progesterone administration (either SC or IV) resulted in an increase in total lordosis duration (TLD) over time. TLD had significantly increased from the pre-progesterone levels by 2 h after 50 μg progesterone IV. In contrast, 50 μg progesterone SC did not cause an increase in TLD until 3 h postinjection. Moreover, in comparison to SC administration, the effects of IV progesterone were short-lived; TLD was significantly decreased by 4 h after injection. Following 200 μg progesterone, the latency to respond was shorter than with 50 μg progesterone (1.5 vs. 2 h). There was no difference in the onset of receptivity as a function of route of administration at the 200 μg dose. These results demonstrate that the minimum latency for the behavioral effects of progesterone is longer in hamsters than has been found in rats. This may reflect species differences in the neurochemical mechanisms of progesterone action.

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Ovariectomized female hamsters received small unilateral implants of estradiol at a variety of anterior-posterior levels of the medial preoptic area and hypothalamus. The results of an initial experiment using 27-ga. implants showed that females with estradiol implants in the ventromedial hypothalamus (VMN) or nearby anterior hypothalamus consistently showed higher levels of sexual receptivity than did females with implants farther rostral, in the preoptic area, or farther caudal, in the posterior hypothalamus. A second experiment used smaller, 28-ga. implants to compare directly the two areas at which implants were effective in the first experiment. The results confirm the findings of other recent studies of hamsters and rats by identifying the VMN as the most effective hypothalamic site for the estrogen priming of sexual receptivity.

The relative effectiveness of progestins for facilitation and inhibition of sexual receptivity in hamsters

In a series of experiments, we studied the biphasic actions of 4 progestins on sexual receptivity in female hamsters. Based on previous reports, we selected doses of progesterone (P), desoxycorticosterone acetate (DOCA), 5-alpha-dihydroprogesterone (DHP) and 20-alpha-hydroxy-progesterone (20-OHP) that were expected to have initial facilitative and/or subsequent inhibitory actions on sexual receptivity. Estrogen-primed ovariectomized female hamsters were given one of 4 doses of a progestin at hour 44 post EB, and were tested for facilitation (with tape over their vaginas to prevent intromissions) 4 hours later. At hour 68, all animals received 500 μg P and were tested for the inhibitory effects of the test progestin 4 hours later. In additional experiments, similar procedures were followed with an alternate vehicle (1% Tween-80 instead of sesame oil) and a longer initial progestin-to-facilitation test interval (8 rather than 4 hours) in attempts to improve bioavailability of the steroids. P and DOCA were clearly the most behaviorally effective progestins tested, and they were equally potent for facilitation and inhibition in an oil vehicle at the 4 hour interval. DHP given in oil caused some inhibition but no facilitation. 20-OHP had no behavioral effects at the doses tested. The results are discussed in light of previous results with these steroids in hamsters and other rodent species. Also, the differing patterns of effectiveness across conditions provide some, although qualified, support for our view that the biphasic actions of progestins may be controlled by separate mechanisms. However, an alternate explanation is also discussed.

Sagittal knife cuts in the far-lateral hypothalamus reduce sexual receptivity in female hamsters

We have previously shown that hypothalamic knife cuts confined to the sagittal plane lateral to the medial anterior hypothalamus-ventromedial nucleus can disrupt sexual receptivity in female golden hamsters. In the present study we have compared the effects of varying the lateral position of sagittal cuts located at this same rostral-caudal level. Near-lateral (NL) cuts were placed at or just lateral to the fornix, while far-lateral (FL) cuts were placed at the lateral edge of the medial forebrain bundle. Ovariectomized, estradiol benzoate plus progesterone-treated females were given weekly tests for lodosis before and after hypothalamic cuts. Changes in body weight and agonistic behavior were also recorded. Both NL and FL cuts reduced lordosis in response to both manual stimulation and a sexually active male. Postoperatively, it was more difficult to elicit lordosis from these females, and if elicited, the duration of the response was reduced. NL, but not FL, cuts also increased agonistic behavior, and produced obesity. Since both NL and FL cuts severed axons traveling in the region of the supraoptic commissures (SOC), these data support our hypothesis that these SOC connections are critical for sexual receptivity. The SOC carry both efferents and afferents of the ventromedial hypothalamus. Sagittal-plane cuts which interrupt the SOC may disrupt lordosis by cutting either or both types of connection.

The excitation and inhibition of sexual receptivity in female hamsters by progesterone: time and dose relationships, neural localization and mechanisms of action.

Ovariectomized hamsters were administered estradiol benzoate (EB) and 44 h later, progesterone (P.) Lordosis behavior was induced. When an additional dose of P was given up to 24 h prior to or 24 h after the EB, EB-P facilitation of lordosis was inhibited. Additional hamsters were given varying doses of P (25-200 mu) following EB using both excitatory and inhibitory paradigms. Inhibition of EB-induced lordosis was effected with a lower dose of P than was the facilitation of EB induced lordosis by P. Hamsters were also given intracerebral implants of P using excitatory and inhibitory paradigms. No excitatory loci were found. Inhibition of EB-induced lordosis was effected by implants in the posterior hypothalamus and anterior mesencephalon, but not by diencephalic implants. Other hamsters were administered tritiated estradiol (E2) plus P prior to, concurrent with, or shortly after the E2. P had no effect upon the accumulation of E2 by any brain sites, although E2 was found to concentrate to a greater degree in the diencephalon than in the mesencephalon or cortex. The estrogen-induced depletion and replenishment of hypothalamic cytosol estrogen receptors was also studied. Concurrent P treatment had no effect upon the receptor depletion-replenishment process. It was concluded that P can both facilitate and inhibit estrogen-induced lordosis and that the inhibitory effects of P are not upon estrogen-sensitive cells in the brain.

Effects of grouping on sexual receptivity in female hamsters.

AbstractFemale hamsters maintained in groups of 4 to 12 animals continue to show four‐day ovulatory cycles. However, when placed with males on the evening of proestrus, only 40% of these grouped females mate. Ninety‐five per cent of females caged singly or in groups of two, mate in less than ten minutes when placed with males on the evening of proestrus. Thus, grouping of female hamsters blocks reproduction in some individuals through a behavioral mechanism which does not apparently affect the ovulatory cycle. Receptivity cannot be reinitiated in such animals by administration of exogenous progesterone on the afternoon of proestrus.

Receptivity in female hamsters following neonatal testosterone, testosterone propionate, and MER-25

One purpose of the present study was to determine the effectiveness of neonatally administered testosterone (T) and testosterone propionate (TP) in suppressing female behavior when their duration of action was equalized. A second aim was to evaluate whether suppression of female capacity associated with neonatal androgen would be lessened by an estrogen blocking agent. Eighty-seven hamsters were assigned to one of 8 groups which had a 3 mm Silastic pellet containing either T or TP as 0, 1, 3, or 9% of its weight present from the second through the tenth day after birth. An antiestrogen, MER-25, or oil was injected from Days 2–10 in another 66 animals that had 0 or 9% T or TP Silastic. Degree of ovarian and behavior suppression was proportional to androgen dosage; at each dosage, T was more effective than TP. MER-25 did not alter suppression produced by either androgen. It was concluded that the comparatively low level of action of exogenous T during development was due to its short half life and that estrogen might not be the hormone mediating suppression of female capacity.