Differential effects of dopamine antagonists infused to the medial preoptic area on the sexual behavior of female rats primed with estrogen and progesterone

Dopamine (DA) in the medial preoptic area (mPOA) is important for the control of appetitive aspects of sexual behavior in the female rat. Recently, following infusions of DA agonists to the mPOA of females primed with estradiol benzoate (EB) alone, we found that the ratio of D1R/D2R activity within the mPOA determines the expression of appetitive behaviors (Graham and Pfaus, 2010). To further the knowledge of this mechanism, the present experiments examined the effects of intra-mPOA infusions of selective DA receptor antagonists. Ovariectomized, sexually-experienced rats primed with EB and progesterone (P) were implanted bilaterally with cannulae aimed at the mPOA and infused with 4 doses (0, 0.25, 1.0 and 4.0 μg) of the nonselective D1R/D2R antagonist flupenthixol (FLU), and selective D1R or D2R antagonists, SCH 23390 (SCH) or raclopride (RAC), respectively, in a randomized order prior to tests of sexual behavior in bilevel chambers. The high dose of FLU significantly decreased solicitations, hops and darts, and pacing behavior. The high dose of SCH also significantly decreased solicitations. In contrast, the high dose of RAC produced an increase in pacing, and a trend toward an increase in solicitations but no other effect on sexual behavior. These results reinforce the idea that the ratio of D1R/D2R activity within the mPOA of female rats is critical for the expression of appetitive behaviors, and further that this ratio is altered by P which shifts the DA effect to a predominantly facilitative D1R activation.     

Effects of total and partial spinal transections on the pudendal nerve-evoked response in rat lumbar axial muscle

The pudendal nerve-evoked activity in lumbar axial muscle nerves 24–48 h following transections was studied in order to examine the supraspinal control of the pudendal nerve-evoked response (PNER). After total transections of the spinal cord in the thoracic region the overall activity in the muscle nerves was much reduced; the evoked responses consisted only of a single peak in activity 19.8 ms (± 1.4 ms) following the last shock of a 3-shock pudendal nerve stimulus demonstrating that some of the earliest responses previously described for the PNER are segmental in origin. To help identify supraspinal inputs to the PNER a series of partial transections were made to cut selectively different fiber columns within the cord. Four different surgical procedures were performed: transections of the entire dorsal half of the cord; ablations of all of the medial columns; combined lesions of the dorsal half and medial columns, sparing the tracts within the ventrolateral columns and bilateral transections of the lateral columns. Following all partial transections except those of the lateral columns, the PNER was similar to that seen in intact animals. After lateral column transections however, the responses were like those seen in the totally transected animals. The combined results suggest that supraspinal influences upon the PNER are conveyed primarily via the ventrolateral columns of the spinal cord. Bilateral convergence of afferent information was evident in the totally transected animals, indicating that such convergence can occur at segmental levels. The lesions which substantially altered the PNER closely paralleled those which eliminated lordotic responsiveness in behaving female rats.     

Ovarian steroid modulation of [H]muscimol binding in the spinal cord of the rat

[³H]Muscimol binding was measured in the lumbar spinal cord of female rats by in vitro quantitative autoradiography. Ovariectomized rats were treated subcutaneously with either oil, estradiol benzoate (EB) or EB plus progesterone (P) in a regime known to reliably induce sexual receptivity. The level of [³H]muscimol binding was highest in laminae I–III and in the region around the central canal. Binding was lower in laminae IV–VI and was frequently undetectable in the ventral horn. There was a significant increase in the level of binding in laminae I–III after EB treatment. There was also a significant increase after treatment with EB+P in comparison to both the ovariectomized and EB-treated groups in this same region of the spinal cord.     

Vomeronasal organ-mediated induction of fos in the central accessory olfactory pathways in repetitively mated female rats

Removal of the VNO significantly reduced the enhancement of lordosis and the induction of fos immunoreactivity in luteinizing hormone-releasing hormone (LHRH) neurons in ovariectomized estrogen-primed rats. There was a significant positive correlation between the two variables. In the accessory olfactory bulb (AOB) of the repetitively mated rats, the number of fos-positive cells in the granule (G) cell layer was significantly lower in the VNO-removed rats, whereas that in the mitral (M) cell layer was not significantly different between VNO-removed and VNO-sham females. The G/M ratio (calculated by dividing the mean number of fos-positive cells in the G cell layer by that in the M cell layer), taken as an estimate of the output of the AOB, was relatively larger in the VN-sham as compared with the VNO-removed rats. There were significant positive correlations between G/M ratio and the increase in LQ and between the G/M ratio and the percentage of fos-positive LHRH cells. The positive correlation between the number of fos-positive cells in the posterodorsal medial amygdala (PDMA) and the increase in LQ and that between the number of fos-positive cells in the PDMA and the percentage of fos-positive LHRH cells were significant, supporting the role of the medial nucleus of amygdala in lordosis. However, the correlation between G/M ratio and the number of fos-positive cells in the PDMA was not significant, indicating that fos immunoreactivity in the PDMA is not directly related to that in the AOB. In conclusion, the results support the involvement of the accessory olfactory system in mediating the facilitatory effects of repeated mating on lordosis in female rats and suggest that the influence of the accessory olfactory system is mediated likely through the LHRH neuronal system. Integration and filtering of sensory information may take place at various levels of the brain, such as the AOB and the medial amygdala, before being transmitted to higher brain centers controlling lordosis behavior in female rats.     

Receptivity,rejection and reactivity in female rats following kainic acid and electrolytic septal lesions

Sprague-Dawley rats were ovariectomized and received bilateral sham, electrolytic or kainic acid lesions of the septum. Kainic acid lesions are purported to destroy cell bodies while not appreciably damaging fibers of passage or afferent terminals. Following priming with estradiol benzoate (EB), animals received three consecutive tests of lordosis and rejection behavior. Animals also received six tests of reactivity; one prior to each EB priming regimen and one following each lordosis and rejection test. Reactivity measures included resistance to capture and magnitude and quantity of startle responses. Electrolytic and kainic acid lesions were equivalent in facilitating lordosis. Although both lesions also increased rejection frequency, kainic acid effects were transient and markedly smaller by 60–80%. Reactivity data generally demonstrated significantly higher scores for kainic acid and electrolytic lesions groups and apparently time-dependent decreases in these scores. The results suggest that rejection behavior is not necessarily correlated with either lordosis or hyperreactivity.     

Facilitation of lordosis behavior in rats by social isolation: Adrenal mediation

Ovariectomized rats were housed either singly or in groups of three, with housing density kept constant. Subcutaneous injections of 0.8 μg estradiol benzoate (EB) were administered daily, beginning 6 days after surgery. The first two experiments provided evidence that isolation facilitated lordosis within 3 days of initial EB administration. Other behavioral components of female sexual receptivity were not affected. The third experiment involved comparison of the effects of isolation in ovariectomized and adrenalectomized-ovariectomized rats. Isolation again significantly facilitated lordosis in ovariectomized rats but no such trend was apparent in adrenalectomized rats even though high levels of lordosis were evident in these animals. One possible interpretation of this latter finding is that isolation of female rats facilitates estrogen-induced lordosis by increasing adrenocortical secretion. The present series of experiments demonstrate that social isolation can influence sexual receptivity in rodents.     

Behavioral consequences of hormonal deprivation on the responsiveness of female rats to estradiol

Female rats which had been ovariectomized either 7 days earlier (short-term deprivation, N = 11) or 35 days earlier (long-term deprivation, N = 11) were tested for their response to treatments of estradiol benzoate (6.0 micrograms/kg body weight) and progesterone (1.2 mg/kg). The long-term deprived females showed less sexual behavior than females deprived for only 7 days prior to treatment. In particular, lordosis quotients after treatment with estradiol alone were significantly lower in the long-term deprived females, t(20) = 3.194, p less than 0.01. Following a supplemental progesterone injection, the lordosis scores and the number of proceptive behaviors displayed by long-term deprived females were also significantly lower than these measures in short-term deprived females, t(20) = 3.481, p less than 0.01 and t(20) = 3.737, p less than 0.01, respectively. In contrast, the two groups did not differ in the degree to which estradiol treatment suppressed food intake, F(1,20) = 2.306, N.S. Likewise, the changes in water intake and body weight produced by estradiol treatment did not differ significantly between the two groups, F(1,20) = 0.118, N.S. and F(1,20) = 0.452, N.S., respectively. The results obtained from the sex behavior tests are generally consistent with the notion that hormonal deprivation alters the responsivity or sensitivity of female rats to estradiol. However, these changes do not appear to involve a general decline in receptor sensitivity or number, because the ability of estradiol to suppress ingestive behaviors was not diminished in the long-term deprived females.     

Hypothalamic knife cuts dissociate maternal behaviors, sexual receptivity, and estrous cyclicity in female hamsters

Female hamsters were tested for their response to pups as virgins, then received sagittal cuts either lateral to the medial preoptic area-medial anterior hypothalamus (anterior cuts) or lateral to the medial anterior hypothalamus-ventromedial nucleus (posterior cuts). Postoperatively females were tested: (a) as virgins, for changes in pup retrieval and cannibalism, (b) for mating behavior, (c) for maternal care and cannibalism of their own pups, and (d) for object hoarding. Anterior cuts converted retrieving virgins to cannibalistic ones and reduced nest builing. All females with anterior cuts cannibalized their litters within a few days of parturition. Half of these females did retrieve pups in home cage tests during the first 3 days postpartum. However, unlike controls, when tested in a neutral arena 5–6 weeks later, no pup retrieval was seen, although most would hoard objects. In contrast, posterior cuts reduced pup retrieval and cannibalism in virgins, and disrupted object hoarding. These cuts did not reduce postpartum pup retrieval, but did reduce postpartum cannibalism. Anterior cuts did not reduce sexual receptivity; posterior cuts reduced sexual receptivity without eliminating ovulation. Anterior cuts are interpreted as having a somewhat selective effect of reducing maternal responsiveness by cutting the lateral connections of neurons in the medial anterior hypothalamus and adjacent medial preoptic area, while posterior cuts disrupt sexual receptivity by cutting lateral connections of the ventromedial hypothalamus which travel in the region of the supraoptic commissures     

Estrogen-induced alterations in synaptic morphology in the midbrain central gray

Summary Axons of ventromedial hypothalamic (VMH) neurons have been previously shown to terminate in the midbrain central gray (MCG) (Chung et al. 1984, 1986). Since VMH synapses in this region may be involved in the mediation of estrogen-induced lordosis behavior, we examined the effect of estrogen on the morphology of synapses in the MCG. Ovariectomized adult female rats were given daily subcutaneous injections of estradiol benzoate (10 g) or the vehicle control and after 20 days of injection, only the estrogen-treated rats showed the lordosis response. A quantitative analysis of MCG tissue from these animals demonstrates morphological changes in various synaptic parameters with estrogen treatment including: 1) an increase in the mean number of dense-cored vesicles and an increase in the number of terminals containing densecored vesicles, 2) an increase in the length of postsynaptic densities (PSDs), 3) an increase in the number of PSDs showing perforations, 4) an increase in the number of synapses, and 5) an increase in the number of synapses with positive synaptic curvature. No alterations in the number of subjunctional bodies were observed. The dense-cored vesicles may contain an estrogen-induced trophic factor which may function in maintaining the integrity of postsynaptic processes and cells in the MCG with which VMN endings contact (Chung et al. submitted) and/or which induces morphological changes in postsynaptic structures which facilitate the effects of estrogen on lordosis behavior.