Effects of progesterone implants in the habenula and midbrain on proceptive and receptive behavior in the female rat

Two brain areas behaviorally responsive to progesterone (P) were examined to determine their possible involvement in the control of rat preceptive behavior, i.e., solicitation behavior directed at the male. Progesterone implants were placed in the habenular nuclei and the interpeduncular nucleus-ventral tegmental area of the midbrain reticular formation (MRF). Different testing procedures and levels of priming with estradiol benzoate (EB) were used in order to distinguish the effects of P in either region on proceptive and receptive behavior during exposure to 10 mounts by stimulus males. To test for receptivity, sexually experienced 60-day-old ovariectomized (ovx) rats bearing stereotaxically placed guide cannulas extending to the habenula or MRF were given 10 μg EB subcutaneously. Forty-eight hours later, lordosis quotient (LQ) was determined. Immediately following this test, each animal was implanted with cholesterol (C) or P and was retested 2 hr later. Treatments for the proceptivity test were similar except that the animals received 2.5 μg EB/100 g body wt sc for 7 days before testing on the eighth day; LQ as well as hopping, darting, and ear wiggling were scored. In the receptivity test, P implantation in both the medial portions of the habenula and the MRF significantly increased lordosis above the levels found both in their preimplantation tests and following control implantation of C. Little proceptivity was observed. In the proceptivity test, P implants in both regions also significantly increased proceptive behavior above both types of control tests. All animals were highly receptive, and there was no difference in LQ among the groups. There was no increase of plasma P levels in similarly implanted animals during a 24-hr monitoring period, indicating that systemic leakage of the hormone was not responsible for the observed behavior. The data indicate that both the habenula and MRF are P-sensitive regions. Progesterone's action on the two areas facilitates expression of both proceptive and receptive components of female sexual behavior, indicating that the neural regulation of the two kinds of behavior is integrated at these levels.     

Neonatal hormonal influences on the development of proceptive and receptive feminine sexual behavior in rats

The objective of this study was to examine the influence of androgen and of the inhibiting of aromatization of androgen to estrogen during the early neonatal period on the development of receptive (lordosis and acceptance of stimulus male mounting attempts) and proceptive (affiliation with and solicitation of stimulus males) feminine sexual behavior. Within 8 hr of birth, male rats were castrated or received subcutaneous implants of the aromatase inhibitor androst-1,4,6-triene-3, 17-dione (ATD) while females received injections of testosterone propionate (TP). At 90 days of age all treated animals and controls were tested for receptive and proceptive feminine sexual behavior. It was found that androgen present neonatally blocked proceptive as well as receptive behavior patterns in adult rats. The proceptive and receptive feminine sexual behavior patterns displayed by adult males deprived of the effects of androgen neonatally either by castration or by treatment with ATD were comparable to those of normal females.     

Dose-response and time-response relationships between progesterone and the display of patterns of receptive and proceptive behavior in the female rat

The relationship between administration of progesterone and the display of patterns of receptive (response to the male) and preceptive (female initiated) sexual behavior was examined in ovariectomized, estrogen-primed female rats in a “restrained male” test situation. It was found that the degree of receptivity and proceptivity displayed was directly proportional to progesterone dose and time from progesterone injection (up to 4.5 hr). Higher progesterone doses and longer period of time from progesterone injection (up to 4.5 hr) were both associated with shorter latencies to return to the male following intromission and ejaculation. Receptivity could be induced with estrogen alone but progesterone was required for the display of proceptivity and higher doses of progesterone were needed to effect increases in proceptivity relative to receptivity. Proceptive behavior also occurred in a narrower time range than did receptive behavior. Receptivity alone is characterized as the lowest degree, and receptivity plus proceptivity as the highest degree, of expression of the total behavior pattern of the estrous female rat. Receptivity and proceptivity together constitute a continuum of estrous responsiveness. Increasing the progesterone dose from 0 to 200 μg, and increasing the latency from progesterone injection from 0 to 4.5 hr, were associated with increasing degree of expression of the total behavioral continuum.     

纳洛酮和大豆黄酮对泌乳早期大鼠血浆LH的影响

32只泌乳期大鼠分成4组,第I组为对照组,第Ⅱ组为纳洛酮组,第Ⅲ组为大豆黄酮组,第Ⅳ组为大豆黄酮及纳洛酮组。结果是,泌乳第12天,与对照组相比,第Ⅱ组与第Ⅳ组血浆LH水平显著提高,第Ⅲ组差异不明显。     

Analeptic and antianaleptic effects of naloxone and naltrexone in rabbits.

Naloxone (5 mg/kg), but not naltrexone, shortened the duration of anaesthesia in rabbits pretreated with pentobarbital. This analeptic effect was blocked by atropine, but not by methylatropine; it thus appears that a central cholinergic mechanism is involved. In contrast, smaller doses of both naloxone and naltrexone attenuated the arousal property of thyrotropin releasing hormone (TRH). Naloxone, but not naltrexone, also antagonized the analeptic property of d-amphetamine. In conscious animals naloxone potentiated, whereas naltrexone attenuated, the excitatory effects of TRH and d-amphetamine.     

Effects of naltrexone on lipopolysaccharide-induced sepsis in rats

Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF- and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF- levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.     

Short-term, postcopulatory changes in receptive and proceptive behavior in the female syrian hamster (Mesocricetus auratus)

The interactions between male and female hamsters were recorded in terms of proximity (approaching, leaving, and following by each member of the pair). The time spent sniffing the partner was also recorded. Mated and unmated females were tested three times on the day of estrus and once on the day following estrus. As expected, receptivity declined rapidly in mated but not unmated females. None of the proximity measures changed during estrus in the unmated females. However, female approaching (Ap% ≈ female approaches as percentage of all approaches) decreased 1–3 hr after mating and was associated with a decline in a number of measures of female proceptive behavior. Female leaving (L% = female leaves as percentage of all leaves) did not change. In unmated females Ap% has decreased and L% has increased by the day after estrus (Day 2 of the estrus cycle). In mated females the decrease in Ap% is accelerated (occurring within the 3 hr after mating) and precedes a change in L% which has occurred by the day after estrus (Day 1 of pregnancy). Thus, mating brings about not only a decrease in receptivity, as has been shown for several species, but also a change in female proceptive behavior and in her stimulus value to the male.     

Onset of the receptive and proceptive components of feminine sexual behavior in rats following the intravenous administration of progesterone

The present study was carried out in order to assess the time course of action of progesterone (P) in the facilitation of complete feminine sexual behavior. Female rats (estrogen primed via 5% E₂ Silastic capsules) were given 200 μg of P either intravenously (iv) or subcutaneously (sc), and tested for estrous behavior at $\text{1}\text{4}$, $\text{1}\text{2}$, 1, 2, and 4 hr after treatment. Among iv-treated animals, significant amounts of lordosis behavior were seen as early as $\text{1}\text{2}$ hr, and a dramatic rise in solicitation behavior was observed at 2 hr. Although sc-treated animals displayed significant amounts of lordosis and solicitation behavior at 2 hr, the behavior was not maximal until 4 hr. Intravenous administration of 400 μg P was equipotent to 200 μg P, whereas 50 μg of iv P was relatively ineffective. A dual mechanism hypothesis pertaining to progesterone's actions in the facilitation of both the receptive and preceptive components of feminine sexual behavior in rats is discussed.     

Androgen-primed castrate males are sufficient for methamphetamine-facilitated increases in proceptive behavior in female rats

Methamphetamine (MA) is a psychomotor stimulant associated with increases in sex drive in both men and women. Women, however, are far more likely to face social disadvantages as a consequence of MA use, and their increased sexual motivation poses additional health concerns such as unplanned pregnancies. To better understand the mechanisms underlying MA-facilitated sexual motivation in females, we previously established a rodent model where a “binge”-type administration paradigm of MA to sexually receptive female rats significantly increases proceptive behavior in the presence of a sexually active, gonadally-intact male. Our previous work with this model has led us to consider whether the increases in proceptive behavior are truly indicative of increased sexual motivation, or instead a consequence of heightened motor responsivity. Here, we test whether MA-induced increases in proceptive behaviors are specific to a sexually relevant stimulus. Females' sexual, social, exploratory behaviors, and interaction times were scored during the exposure to stimulus males, including castrates, and dihydrotestosterone (DHT)-treated castrates. MA-treated females demonstrated significant increases in proceptive behaviors toward DHT-treated castrate males but not toward castrate males. While the non-MA-treated females did display proceptive behavior, there was no significant difference between behaviors elicited by DHT-CX males compared to CX males. Our results support the hypothesis that MA facilitates proceptive behavior only in response to specific, androgen mediated sexually-relevant cues.     

The effects of estrogen and progesterone on female rat proceptive behavior

The relative importance of estrogen (EB) and progesterone (P) in stimulating proceptivity in ovariectomized female rats was studied. Proceptive behavior was measured quantitatively, providing a clear measure of response to experimental manipulation. When rats were tested biweekly after daily treatment with 0.4 μg/100 g body wt EB for 4 days, they showed maximal lordosis but low levels of proceptive behavior by the second test. Additional EB (3.0 μg/100 g body wt daily) failed to stimulate additional proceptivity. A graded increase in proceptive behavior resulted from administration of increasing doses of P (50, 100, 500 μg and 1.0 mg) to animals receiving EB priming as described above. The level of “soliciting” was significantly higher than EB-only-treated rats when 500 μg or 1.0 mg P was given. Ovariectomized, adrenalectomized rats, primed with 2.5 μg/100 g body wt EB daily for 7 days and tested on Day 8, were significantly less proceptive than ovariectomized, sham-adrenalectomized rats with the same hormone treatment. Four hours after injection of 1.0 mg P, there was no difference in proceptive or receptive behavior between sham- and adrenalectomized rats. It was concluded that if an EB dose is sufficient to induce maximal receptivity, additional estrogen does not stimulate proceptivity; unlike previous studies, the present data are not consistent with a global effect of ovarian steroids on both components of female behavior. Progesterone is more effective than estrogen in stimulating proceptive behavior, although proceptivity is not absolutely dependent on progesterone for expression. Proceptivity in EB-only-treated rats appears to be facilitated by adrenal P.     

Hysterectomy facilitates proceptive behavior in rats

The effects of hysterectomy on proceptive behavior were investigated using several doses of estradiol benzoate (EB) and progesterone (P) in female rats. One week after surgery, ovariectomized (OV) and ovariectomized-hysterectomized (OH) rats were given three daily injections of 1.0 or 2.0 micrograms EB followed by 0.5 mg P or oil on the fourth day and were tested for solicitation 4 hr later. The same animals received 1.0 or 2.0 micrograms EB plus 0.1 mg P, or 4.0 micrograms EB plus oil on the same schedule a week following the first test and were tested again. Ovariectomized-hysterectomized animals receiving 0.5 mg P, regardless of the EB dose, showed significantly higher solicitation scores than OV animals, but the scores of the EB-primed OV and OH rats receiving 0.1 mg P or oil vehicle did not differ.     

Effects of intracerebroventricular leptin administration on feeding and sexual behaviors in lean and obese female Zucker rats

Obese Zucker rats (fa/fa) are characterized by inadequate leptin signaling caused by a mutation in the leptin receptor gene. Obese Zucker females are infertile and hyporesponsive to the inductive effects of ovarian hormones on sexual behaviors. Leptin treatment reverses aspects of reproductive dysfunction due to perturbations in energy balance in other animal models. Our first experiment tested the hypothesis that intracerebroventricular (icv) leptin administration would enhance the display of sexual behaviors in obese Zucker females. A second experiment compared lean and obese Zucker females' responses to leptin, during fed and fasted conditions. Ovariectomized (OVX) Zucker rats were implanted with lateral ventricular cannulae. In Experiment 1, fasted, obese females received estradiol benzoate, progesterone, and icv injections of 3, 18, or 36 microg murine leptin or vehicle. Leptin administration reduced food intake, but did not enhance sexual behaviors. In Experiment 2, steroid-replaced, OVX lean and obese females (from a different source than those in Experiment 1) received icv injections of vehicle or 3 or 36 microg leptin under fed and fasted conditions. Leptin treatment reduced food intake and weight gain in the fed, but not the fasted, condition in both genotypes. Sexual receptivity and locomotion were not affected, but icv leptin injections reduced proceptive behaviors in ad libitum-fed rats. These data confirm previous reports that centrally administered leptin decreases food intake and weight gain in obese Zucker rats; results from Experiment 2 suggest that lean and obese females are similarly responsive to these actions of leptin. Contrary to our hypothesis, leptin treatment did not stimulate sexual behaviors; rather, the hormone appears to inhibit the display of sexual proceptivity in ad libitum-fed lean and obese Zucker female rats.     

Display of proceptive behaviors in relation to urinary and fecal progestin levels over the ovarian cycle in female tufted capuchin monkeys

In many primates species, female sexual attractivity is influenced by behavioral cues as well as by nonbehavioral cues (i.e., visual-morphological or chemical signals). Both kinds of cues are usually related to the ovarian cycle and female hormonal state. Female tufted capuchins (Cebus apella) lack any external morphological change in relation to the ovarian cycle and evidence of scent-marking behavior has never been reported. In addition, tufted capuchin males do not routinely investigate the female's body or urine. Instead, capuchin females are extremely active in sexually soliciting the male(s) and their courtship toward them involves a rich behavioral repertoire. In the present study we defined female tufted capuchin proceptivity and investigated its relationship with female reproductive state. Ovarian hormones were measured in urine and fecal samples from four captive females in order to (a) assess their reliability for monitoring female ovarian function and (b) provide information on the timing of the component cycle phases and in particular the periovulatory phase. Measurements of urinary and fecal progestin metabolites provided the best indicator of ovarian cyclicity and for timing of the periovulatory phase. Through a multivariate analysis of the behavioral data set we distinguished four behaviors (eyebrow raising with vocalization, touching-and-running, nuzzling and head cocking) which showed a marked cyclicity (21.3 days) that matched that of urinary progesterone (21.9 days). Data showed that each period of proceptive behaviors was 2.7 +/- 0.8 days long and the day of a defined luteal phase rise in urinary progesterone levels was markedly shifted toward the end of this period. Furthermore, the ejaculations observed always occurred within proceptive periods. The results clearly indicate that female behavior is a good indicator of the periovulatory phase and can enhance female attractivity.     

Apparent pA2 value of naltrexone is not changed in rats following continuous exposure to morphine or naloxone.

Chronic opioid antagonist administration increases opioid binding sites and potentiates behavioral responses to morphine. Conversely, chronic opioid agonist administration attenuates behavioral responses to morphine, though this is not necessarily accompanied by a parallel loss of binding sites. We examined the possibility that the in vivo affinity of the mu receptors might be altered as a consequence of the continuous administration of either naloxone or morphine. Rats were implanted sc with naloxone- or morphine-filled osmotic pumps; control animals were implanted with sham pumps. One week later, 24 hr after removing the osmotic pumps, cumulative dose-response curves for fentanyl analgesia were generated in the presence of 0.0, 0.03, 0.1, or 0.3 mg/kg naltrexone, using a tail-flick procedure. The analgesic ED50 (with 95% C. L.) of fentanyl in sham implanted animals, following saline pretreatment was 0.027 mg/kg (0.019, 0.039). The potency of fentanyl was decreased in rats infused with morphine, ED50 = 0.051 mg/kg (0.028, 0.093), and increased in rats that received naloxone, ED50 = 0.018 mg/kg (0.015, 0.022). The mean apparent pA2 value for naltrexone (with 95% C.L.) in the control group was 7.7 (7.5, 7.9). No differences were detected in animals that had received either naloxone or morphine for 7 days, pA2 = 7.8 (7.5, 8.1) and 7.4 (7.3, 7.6), respectively. Our results indicate that there is no change in the apparent affinity of the mu-receptor following continuous exposure to either an opioid agonist or antagonist, at a time when the analgesic potency of the agonist is decreased or increased, respectively.     

Prostaglandin E2 induces receptive behaviors in female Xenopus laevis

The object of this study was to examine the effects of exogenous and endogenous prostaglandin E2 (PGE2) on the sexual behavior of female South African clawed frogs, Xenopus laevis. Ticking and leg extension, which communicate sexual unreceptivity to males, were studied in intact, ovariectomized, and ovariectomized-oviductectomized females. The onset of the PGE2 behavioral effect occurs within 30 sec to 3 min of injection for intact and ovariectomized females; for ovariectomized-oviductectomized females, the latency period for the effect ranges from 10-20 min. PGE2 induced receptivity in doses as low as 0.03 microgram/frog. Injection of the prostaglandin synthesis inhibitors, indomethacin and flurbiprofen (FBP), blocked chorionic gonadotropin- (HCG-) induced behavioral receptivity, suggesting that endogenous prostaglandin synthesis may have a role in regulating female sexual behavior. Flurbiprofen blockade of HCG-induced receptivity was reversed by PGE2 administration, suggesting that FBP's effects are PG synthesis-specific.     

Effects of naloxone on pethidine-induced neonatal depression. Part I--Intravenous naloxone.

Infants whose mothers had had pethidine during labour were given either naloxone 40 microgram or isotonic saline administered intravenously double-blind within one minute of birth. Peak alveolar carbon dioxide tension, carbon dioxide excretion, alveolar ventilation, feeding behaviour, and habituation to a specific sound stimulus were measured regularly up to 48 hours after birth. Alveolar carbon dioxide tension was significantly lower and alveolar ventilation significantly higher half an hour after birth in the naloxone-treated group than in the saline-treated group, but these differences between the groups were not significant at any other time, and there were no significant differences in sucking frequency or pressure, milk consumption, or habituation to the auditory stimulus.     

Effects of naloxone on pethidine-induced neonatal depression. Part II--Intramuscular naloxone.

Thirty full-term infants whose mothers had had pethidine during labour were given either naloxone 200 microgram or normal saline intramuscularly. The drugs were chosen blindly and administered within one minute of birth. Naloxone produced a significant reduction in mean alveolar carbon dioxide tension and an increase in carbon dioxide excretion and mean alveolar ventilation at all times up to 48 hours after birth. The mean rate of habituation to a repeated auditory stimulus, the mean sucking frequency, the sucking pressure, and the mean consumption of milk were all significantly higher in the naloxone-treated group than in the placebo-treated group up to 48 hours after birth. Intramuscular naxolone therefore seemed to reverse the undesirable effects of pethidine.     

Cardiovascular effects of naloxone,naltrexone and morphine in the squirrel monkey

Heart rate (HR) and mean arterial blood pressure (BP) were recorded from conscious, chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous injections of two opiate antagonists and an agonist. Naloxone (0.3–10.0 mg/kg) or naltrexone (0.3–10.0 mg/kg) had little effect on HR or BP during a 30-minute post-injection period. Morphine (3.0–5.6 mg/kg) produced biphasic effects comprising an initial decrease followed by an increase in HR, and an increase followed by a decrease in BP. Lower morphine doses had lesser effects during a 100-minute post-injection period. Pre-treatment with 0.03 mg/kg naloxone attenuated the depressive effect of morphine on HR and BP, but increases in HR and BP due to morphine were enhanced. Pretreatment with 0.3 mg/kg naloxone prevented morphine-induced decreases in HR and BP, yet increases in HR and BP persisted. In previous behavioral studies, morphine in combination with naloxone similarly increased rates of responding in the squirrel monkey. Together, these data suggest an effect of naloxone that goes beyond mere pharmacological antagonism of the effects of morphine.