Nitric oxide mediates sexual behavior in female rats

Nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation, cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located in the hypothalamus. These NOergic neurons control the release of several hypothalamic peptides. Release of NO from these NOergic neurons stimulates pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and LHRH release in vitro. LHRH not only induces LH release, which induces ovulation, but also facilitates female sexual behavior. Sexual behavior can be induced reliably in estrogen-primed ovariectomized female rats by progesterone (P). This behavior consists of proceptive behavior to attract the male and the assumption of a clear characteristic posture, lordosis, when mounted by the male. To ascertain the role of NO in the control of sexual behavior in female rats, an inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P-facilitated lordosis when administered intracerebroventricularly into the 3V, 20 min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not inhibit NOS, did not inhibit lordosis under the same experimental conditions. Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously releases NO, facilitated lordosis in estrogen-primed rats in the absence of P. The facilitation of lordosis induced by either P or SNP was prevented by intracerebroventricular injection of hemoglobin, which binds NO. Lordosis facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V. The results are interpreted to mean that the P-facilitated lordosis response is mediated by LHRH release. Furthermore, since NO release from SNP also facilitates lordosis in the absence of P and this response could be blocked by LHRH antiserum, we conclude that P brings about the release of NO, which stimulates LHRH release that facilitates lordosis. Thus, the results indicate that NO induces LHRH release and that LHRH then plays a crucial role in mediation of sexual behavior in the female rats.     

Hypophysectomy facilitates sexual behavior in female rats

Lordosis was elecited in 49% of 87 hormonally untreated, hypophysectomized-ovariectomized (hypox-ovx) female rats in response to palpation of the flanks and perineum (vaginal stimulation was not applied). By contrast, only 12% of 113 hormonally untreated ovariectomized (ovx) rats showed lordosis in response to such stimulation. Subsequently, hypox-ovx and ovx-only rats were given daily injections of 1 mug/kg estradiol benzoate (EB) and tested for sexual receptivity with males. Teh estrogen-treated hypox-ovx females became sexually receptive significantly earlier, and exhibited higher lordosis quotients and more soliciting behavior, than the estrogen-treated ovx-only rats. The increased sexual responsiveness in the hypox-ovx rats could be due to increased LRH activity. To test this, we treated hypox-ovx rats with dihydrotestosterone propionate (DHT-P), which suppresses plasma LH levels but is relatively ineffective in inducing sexual receptivity, and found a significant depression of lordosis responsiveness. These experiments suggest that hypox-ovx females show a heightened responsiveness to hormonal and/or sensory factors that induce a lordosis response, possibly because of increased LRH activity.     

Assuring quality, information, and choice in managed care

The aim of the study was to determine whether there is an increase in responsiveness to estrogen stimulation of maternal behavior and lordosis responsiveness during pregnancy. Using separate groups of pregnancy-terminated females, we measured the initial maternal responsiveness of hysterectomized-ovariectomized (HO) females and their responsiveness to estrogen stimulation. Maternal behavior latencies were studied in females HO on the 8th, 10th, 13th, 16th, or 19th day of pregnancy (8HO-19HO) and in nonpregnant HO (NPHO) females. Groups were injected sc with estradiol benzoate (EB) in doses ranging from 0 to 200 microgram(s)/kg and tested for maternal behavior (retrieving, crouching, and licking pups). In addition, we investigated whether there is an increase during pregnancy (following HO) in lordosis responsiveness to estrogen stimulation. Lordosis behavior was studied in pregnant HO females (days 8, 16, and 22) and NPHO females given 0 to 200 microgram(s)/kg EB. There was an increase in maternal responsiveness in oil-treated HO females starting around midpregnancy. From early pregnancy on there was also an increase in maternal responsiveness to 20 microgram(s)/kg EB. In late pregnant females (16HO) there was a further increase with 50 microgram(s)/kg EB. There was no increase in lordosis responsiveness to EB stimulation during pregnancy; pregnant and nonpregnant HO females had the same EB threshold for stimulating lordosis behavior. The results of both studies were related to increases during the latter half of pregnancy in nuclear estrogen receptor concentrations in the MPOA, an area that mediates estrogen stimulation of maternal behavior, and the absence of such increases during pregnancy in the VMH, an area that mediates estrogen stimulation of lordosis behavior.     

Effects of repeated testing on sexual behavior of the female rat.

Investigated effects of stimulation during repeated testing, using 24 female Sprague-Dawley rats in which intromission was prevented by a vaginal mask. Ss were ovariectomized and administered 1 mg of estradiol benzoate (EB) daily for 10 days (Exp I) or 5 mg of EB for 2 days (Exp II). Behavioral indices included lordosis quotient (a measure of sexual receptivity) and rejection quotient (a measure of social rejection of the male). Intensity and duration of lordosis gave additional measures. In Exp I hourly testing increased lordosis quotient and duration, especially in Ss receiving EB for 5 days; no effects of daily testing were shown. Exp II compared the behavior of Ss that were either handled hourly and tested hourly with the male rat or only handled hourly to the behavior of Ss that were tested and handled only once. Repeated testing and/or handling facilitated sexual responsiveness, while Ss that received neither treatment were sluggish in their social response to the male rat when they were tested, and were not sexually receptive. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heterotypical sexual behavior in male rats: individual difference in lordosis respones

Castrated Wistar male rats were primed with varying amounts of estradiol benzoate (EB) for successive 2 days and progesterone (P) on the third day 6-8 hr prior to the behavioral test. The tests were performed 4 times at 2-3 weeks intervals. As a priming procedure for the first behavioral test, 50 mug EB and 0.5 mg P were given. The quantity of P was kept constant therafter. For the second test, the dose of EB was increased to 100 mug, but decreased again to 50 mug and further to 10 mug for the third and fourth tests, respectively. The inciedence of animals showing lordosis was quite low, and was not significantly changed by increasing or decreasing the dosage of EB during the series of the behavioral tests. Forty-three out of 51 animals never showed lordosis at all 4 behavioral tests. In contrast, 5 out of 8 rats which responded to mountings by the males continued to display lordosis behavior throughout the series of the successive 4 tests. This consistence of individual responeses during the series of the behavioral tests may indicate the possible existence of individual difference in lordosis responde in male rats.     

A serotonin-4 receptor-like pseudogene in humans

Serotonin (5-HT) receptor interaction in the control of female rat lordosis behavior was examined. Ovariectomized rats, with bilateral implants in the ventromedial nucleus of the hypothalamus (VMN), were hormonally primed with 25 micrograms estradiol benzoate and 500 micrograms progesterone. Rats were infused with the 5-HT3 receptor antagonist, 3-tropanyl-indole-3 carbonylate (tropisetron; 500 ng), or were coinfused with the 5-HT3 receptor antagonist and the 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 500, 1500, or 2000 ng). Additional ovariectomized, hormone-primed rats received bilateral VMN infusions with the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 200 ng), or were coinfused with the 5-HT1A receptor agonist and the 5-HT3 receptor agonist, m-chlorophenyl-biguanide (mCPBG; 250, 500, or 1000 ng). Lordosis behavior was observed prior to VMN infusion, during the infusion and for 30 consecutive minutes thereafter. Tropisetron reduced the lordosis to mount (L/M) ratio in every animal investigated but the decline was attenuated by coinfusion with DOI. Similarly, the L/M ratio declined following infusion with 8-OH-DPAT and the decline was dose-dependently reduced by coinfusion with mCPBG. Only the 5-HT3 receptor agonist altered the quality of the lordosis reflex. These studies provide evidence that the effects of 5-HT on female rat lordosis behavior involve the integrated activity of at least 3 different 5-HT receptor families.     

Concurrent inhibition of sexual behavior, but not brain [–3H]estradiol uptake, by progesterone in female rats.

In 7 experiments with ovariectomized female Sprague-Dawley rats, chronic injections of high doses of progesterone (5 mg) and low doses of estradiol benzoate (EB; 2 μg) resulted in less sexual behavior than did low doses of progesterone (.5 mg) and low doses of EB. In a typical procedure for inducing sexual behavior, EB and progesterone were given sequentially, separated by 42 hrs. High levels of progesterone (2.5 and 5 mg) administered concurrently with EB inhibited the induction of sexual receptivity. Increasing the dose of EB from 2 μg to 6 μg or 10 μg offset this inhibition. High doses inhibited the induction of sexual behavior, but the inhibition waned when progesterone was administered 48 hrs prior to EB. A single injection of progesterone (1 mg) that did not inhibit the induction of sexual behavior when administered concurrently with EB did inhibit lordosis when distributed into 5 injections (.2 mg) every 4 hrs. Results of 2 experiments in which progesterone did not inhibit the uptake or retention of [–3H]estradiol by brain cell nuclei suggest that the antiestrogenic action of progesterone in the CNS is not to interfere with the binding of estradiol. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Facilitation of female rat lordosis behavior by hypothalamic infusion of 5-HT(2A/2C) receptor agonists

Ovariectomized rats were hormonally primed with 0.5 microg estradiol benzoate and 500 microg progesterone to produce two groups of rats differing in their lordosis behavior. Females with a lordosis to mount (L/M) ratio < 0.5 were used to test the hypothesis that 5-HT(2A/2C) receptor agonists could facilitate lordosis behavior. Females with L/M ratios > or = 0.5 were used to evaluate the potential suppressive effect of 5-HT(2A/2C) receptor compounds. Lordosis behavior was examined following bilateral infusion of drugs into the ventromedial nucleus of the hypothalamus (VMN). Drugs examined were the 5-HT(2A/2C) receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), the 5-HT(2A/2C) receptor antagonist, 3-[2-[4-(4-fluorobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quinazoli nedione tartrate (ketanserin tartrate), and the non-selective 5-HT receptor agents, 2-(1-piperazinyl)quinoline dimaleate (quipazine) and N-(3-trifluoromethylphenyl)piperazine HCl (TFMPP). Drugs with agonist action at 5-HT(2A/2C) receptors increased lordosis behavior in rats with low sexual receptivity. The 5-HT(2A/2C) receptor antagonist, ketanserin, inhibited lordosis behavior in sexually receptive rats. DOI attenuated the lordosis-inhibiting effect of ketanserin, but ketanserin was less effective in preventing DOI from increasing lordosis behavior. These results strengthen prior inferences that activation of 5-HT(2A/2C) receptors can facilitate lordosis behavior and that the VMN is one site at which such facilitation can occur.     

Inhibition of lordosis in rats by the antiestrogen CI-628 in the absence of progesterone.

Assessed whether the ability of the antiestrogen CI-628 to inhibit estrogen-stimulated lordosis behavior (LB) in adult ovariectomized Sprague-Dawley rats depends on its interference with the synergistic effects of estrogen with progesterone. In Exp I the effect of CI-628 was contrasted in Ss brought into estrus by estradiol benzoate (EB; 0 or 3 μg/.1 ml) combined with progesterone (P; 42 or 500 μg/.1 ml) vs 4 daily injections of EB (without P). CI-628 effectively antagonized LB in both conditions. In the absence of CI-628, Ss receiving P had significantly higher LB scores than the 4-day EB controls. In Exp II Ss receiving CI-628 on only the 1st 2 of 4 days of EB injections had decreased LB scores unless P was also given on the day of testing. This suggested that the EB from the latter injections was not acting as a progestin "mimic." In Exp III LB stimulated by EB (without P) was inhibited by CI-628 in Ss that were both ovariectomized and adrenalectomized. This suggested that adrenal progestins were not involved in the ability of CI-628 to inhibit LB. Results suggest that the mechanism of action of CI-628 for the inhibition of LB does not depend on its ability to antagonize an estrogen-induced increase in neural progestin receptors. Implications for estrogen-mediated behaviors, for which CI-628 has little or no antagonistic effects, are discussed. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of thyroxine and estrogen on the expression of estrogen receptor alpha, cholecystokinin, and preproenkephalin messenger ribonucleic acid in the limbic-hypothalamic circuit

To study thyroid hormone and estrogen interactions in the central nervous system (CNS), the expression of estrogen sensitive genes was examined within the limbic-hypothalamic circuit. Estrogen up-regulates the expression of reproductively relevant neuropeptide messenger RNAs (mRNAs) encoding cholecystokinin (CCK) and enkephalin, peptides that stimulate lordosis. Estrogen down-regulates the expression of the estrogen receptor alpha (ER alpha) mRNA in the nuclei of the circuit. We examined the possibility that thyroid hormone treatment would block the estrogen modulation of these messages. Estradiol benzoate (EB), EB + thyroxine (T4), T4, or oil were administered to ovariectomized, adult female rats for 10 days. Isotopic in situ hybridization histochemistry revealed that within the limbic-hypothalamic nuclei, levels of CCK and preproenkephalin (PPE) mRNA levels were significantly higher in EB and EB + T4-treated animals compared with T4 or oil-treated animals. ER alpha mRNA levels were low in EB treated animals, elevated in T4 or oil-treated animals and further elevated in EB + T4-treated animals. In summary, T4 treatment had neither an independent nor an antagonistic effect on estrogen induced expression of CCK or PPE mRNA in the circuit. However, T4 did prevent the normal estrogenic decrease of ER alpha mRNA levels in the nuclei of the limbic-hypothalamic circuit.     

Estradiol benzoate facilitates lordosis and ear wiggling of 4- to 6-day-old rats.

The effects of exogenous and endogenous steroids on components of female sexual behavior of neonatal male and female rats were investigated. In Experiment 1, 4-day-old rats were treated with 0, 0.1, 1.0, 10, or 100 μg/10 g body weight estradiol benzoate (EB) and were tested 44 hr later. In Experiment 2, male rats castrated within 24 to 48 hr of birth were compared with sham operated controls and castrates given steroid replacement. The results indicated that most 6-day-old pups will display lordosis and ear wiggling, therefore, the display of these responses is not dependent upon exogenous steroids. However, a fine-grain behavioral analysis revealed that EB treatment increased the frequency, duration, and intensity of lordosis and the frequency of ear wiggling in infant females, and it increased lordosis duration in males. Castration of infant males decreased the likelihood that male infants would display lordosis, whereas testosterone replacement restored behavior to control levels. These data question the concept that organizational and activational actions of estrogens occur during completely separable times in development and should provide new insights into the development of estrogen receptor function and the process of sexual differentiation of brain and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of ovarian secretions on female behavioral potentiality in the rat.

Measured receptivity in female Sprague-Dawley rats ovariectomized at 5 ages, in neonatally gonadectomized females and males implanted with ovaries, and in neonatally castrated males injected with estradiol benzoate (EB) or oil. Mean receptivity, darting, and lordosis scores were higher during the 1st 4-5 mating tests in females and males having ovaries prepubertally. In amounts greater than .01 mg., EB inhibited female behavior. Even after ovariectomy, body weight was lightest in males and females having ovaries for 60 days. Progesterone and EB decreased weight gain faster in Ss gonadectomized prepubertally. Results indicated that physiological amounts of ovarian hormones, while not necessary for development of female potentiality, permanently influence it by modifying rate of utilization of estrogen circulating during adulthood. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hysterectomy on sexual receptivity, food intake, running wheel activity, and hypothalamic estrogen and progestin receptors in rats.

Ovariectomized-hysterectomized (OH) CD rats given sequential treatments with 2 μg of estradiol benzoate (EB) and .5 mg of progesterone (P) showed significantly higher lordosis quotients than ovariectomized (OV) Ss in 2 tests, 1 and 2 wks after surgery. To test whether the effects of hysterectomy persist, 3 groups of OV and OH Ss received weekly injections of EB, EB?+?P, or sesame oil for 4 wks, were given 2 μg of EB followed 24 hrs later by .5 mg of P, and tested for receptivity. Only the OH Ss that had received hormones for 4 wks showed a significantly higher lordosis score than OV Ss. The effects of hysterectomy on food intake, weight gain, and running wheel activity were also tested. After 1 wk of 2 μg/day EB, OH Ss lost significantly more weight and consumed less food than OV Ss, but by 2 wks the effects of hysterectomy were no longer evident. Treatment with .5 μg/day EB resulted in a significant loss in weight and food intake in OH Ss throughout the experiment. OH Ss implanted with Silastic capsules containing EB were significantly more active in running wheels than OV Ss over the 1st 9 days, but by Day 23 the activity of both groups was similar. 24 hrs following a single injection of EB, hypothalamic-preoptic area cell nuclear estrogen receptors and cytoplasmic progestin receptors were significantly higher in OH than in OV Ss. Possible mechanisms by which hysterectomy might act to enhance hormone-dependent behaviors are discussed. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain transections differentially alter lordosis and ear wiggling of 6-day-old rats.

The involvement of various brain regions in lordosis and ear-wiggling, which resemble components of adult female sexual behavior, was examined by making acute transections along the neuraxis from the olfactory tract to the medulla in 6-day-old rats. Four to 5 hrs after the transection procedure, pups were tested for lordosis and ear wiggling. Lordosis was reduced or eliminated in pups with cuts through the hindbrain or diencephalon (above the level of the mammillary bodies) but was relatively unaffected by cuts through the posterior hypothalamus and rostral tegmentum and by cuts rostral to the anterior hypothalamus. Ear wiggling was disrupted by transections throughout the hindbrain and was facilitated only in females by transections throughout the forebrain (anterior to the mammillary bodies). Data suggest that facilitation from the hypothalamus is required for lordosis in the infant rat and the forebrain inhibitory systems for ear wiggling are functional in female infants by 6 days of age. Similarities and differences between the neural control of lordosis and ear wiggling in infant and adult rats suggest that the infant sex-like behaviors may be precursors of adult female sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence that a factor besides progesterone, prolactin, or plasma-estradiol-binding protein inhibits estrogen-induced sexual receptivity in pregnant rats.

Reexamined in 4 experiments the assumption that progesterone is responsible for the inhibition of estrogen-induced receptive behavior in Wistar hooded rats. Daily administration of estradiol benzoate (EB) stimulated significantly less lordotic behavior during the 2nd half of pregnancy than in ovariectomized Ss that received sc progesterone implants, pituitary grafts that raised plasma prolactin, or both treatments combined. Following an initial facilitation of receptivity, Ss with progesterone implants showed only moderate reductions in lordosis quotients over 3 test days. The capacity of Ss' plasma to bind estradiol was found to increase significantly during the 2nd half of pregnancy. However, daily administration of a synthetic estrogen, R 2858, which is not bound by plasma protein, was no more effective than EB in stimulating receptive behavior. Administration of EB also stimulated significantly lower levels of sexual behavior in pregnant Ss than in Ss in which pseudopregnancy had been prolonged by previous hysterectomy or induction of uterine decidualization. These findings suggest that some endocrine factor other than progesterone, prolactin, or estradiol-binding protein is primarily responsible for the potent suppression of behavioral responsiveness to estrogen that occurs in pregnant rats. It is suggested that 5-alpha-reduced androgens may cause these behavioral effects. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female lordotic behavior mediated by monoamines in male rat.

In Exp I direct application of serotonergic or b-adrenergic receptor blockers to anterior or posterior areas of the hypothalamus induced lordosis in 18 intact estrogen-primed male Sprague-Dawley rats. Such treatment with an a-adrenergic blocker or systemic administration of progesterone failed to increase lordosis. In Exp II (n = 7) centrally elicited lordosis did not occur without estrogen priming. It is concluded that anatomical and neurochemical similarity may exist in the brain mechanism mediating lordotic behavior in male and female adult rats. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of coital stimulation upon behavior of the female rat.

Tested the importance of vagino-cervical stimulation during coitus in 2 experiments, using 16 intact and 48 ovariectomized Sprague-Dawley female rats, in which intromission was prevented by a vaginal mask. The behavior of Ss was compared to that of unmasked females. Behavioral indices included lordosis quotient, a measure of sexual responsiveness, and rejection quotient, a measure of social response toward the males. The rating of lordosis intensity on a 3-point scale provided a mean lordosis intensity. Exp. I investigated long-term effects of coital stimulation by repeated testing of Ss in natural and hormone-induced heat. Coital stimulation generally decreased the probability of subsequent lordosis and increased display of rejection. Exp. II studied the short-term effects of coital stimulation using single 50-mount tests. Coital stimulation decreased intensity as well as probability of subsequent lordosis. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular genetic analysis of DNA structure of pFra plasmids in plague pathogen of varying biovar]

OBJECTIVE: To clarify the mechanism of the suppressive effect of 2-buten-4-olide (2-B4O), an endogenous feeding suppressant, on the pulsatile secretion of luteinizing hormone (LH), by studying whether endogenous opioid peptides are involved in this suppressive effect. METHODS: Using ovariectomized (ovx) rats, blood samples were taken every 6 min for 2 h after administration of 2-B4O or saline into the third cerebroventricle (3V) and sequential i.v. injection of naloxone (0. 5 mg/kg per h) or saline. Rats were divided into three experimental groups: group 1: 3V saline + i.v. saline (control); group 2: 3V 2-B4O + i.v. saline; group 3: 3V 2-B4O + i.v. naloxone. Serum LH concentrations were determined by double-antibody RIA. To determine whether 2-B4O affected the biosynthetic activity of the opioidergic neurons within the ovx rat arcuate nucleus, we measured the concentrations of pro-opiomelanocortin (POMC) mRNA, a precursor of beta-endorphin, in the rostral arcuate nucleus using non-radioactive in situ hybridization and a computerized image-analysis system. RESULTS: 2-B4O significantly suppressed the pulse frequency of LH (group 2: 1.5+/-0.33 pulses/2 h, group 1: 2.43+/-0.2 pulses/2 h; P < 0.05), but naloxone blocked its suppressive effect and restored the pulse frequency (group 3: 3.29+/-0.36 pulses/2 h, group 2: 1.5+/-0.33 pulses/2 h: P < 0.01). There were no significant changes in the mean LH concentrations and amplitude. Furthermore, 2-B4O significantly stimulated the expression of POMC mRNA in the rostral arcuate nucleus. CONCLUSION: These results suggest that 2-B4O may impair the pulsatile secretion of LH by activating the opioid pathway within the hypothalamus.     

Brain beta-endorphin and other opioids are involved in restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system, and the adrenal medulla in the rat

Opiates and opioids have complex effects on the hypothalamic-pituitary-adrenal axis, and they stimulate the sympathetic nervous system. This study was designed to clarify the role of brain beta-endorphin in the mechanism by which stress increases plasma concentrations of adrenocorticotropin (ACTH), epinephrine (E), and norepinephrine (NE). Intracerebroventricular (i.c.v.) administration of beta-endorphin to rats significantly increased plasma ACTH levels at doses of 0.09, 0.3, and 1.5 nmol, and plasma E and NE levels at doses of 0.3 and 1.5 nmol. The rise of plasma ACTH, E, and NE levels by 0.3 nmol beta-endorphin was inhibited by intravenous (i.v.) administration of 2 mg/kg b.wt. naloxone. I.v. administration of anti-rat corticotropin-releasing hormone (CRH) rabbit serum completely blocked the beta-endorphin-induced ACTH secretion without affecting the secretion of E and NE. I.c.v. administration of anti-beta-endorphin rabbit gamma-globulin attenuated a 30-min restraint stress-induced rise of plasma ACTH levels without significant influence on the rise of E and NE levels, whereas i.v. administration of naloxone attenuated the restraint stress-induced rise of plasma ACTH, E and NE levels. These results suggest that i.c.v. administration of beta-endorphin stimulates the secretion of ACTH, E, and NE through opiate receptor, and that brain CRH mediates the beta-endorphin-induced secretion of ACTH. The results also suggest that brain beta-endorphin is, at least in part, involved in the restraint stress-induced stimulation of the hypothalamic-pituitary-adrenal axis, and that some opioids other than beta-endorphin are involved in the stimulatory mechanism of the autonomic nervous system and the adrenal medulla in the rat.     

Expression of the conditioned NK cell activity is beta-endorphin dependent

We are interested in identifying the pathways which are responsible for triggering the conditioned enhancement of natural killer (NK) cell activity. Earlier studies have suggested that central opioid(s) are involved in eliciting the expression of the conditioned NK cell activity. The purpose of this study was to identify the central opioid peptides that allow the central nervous system (CNS) to communicate with the immune system. Mediators that activate the efferent pathway of communication between the CNS and immune system was examined by injection of the mediator via the cisterna magna (CM). Conditioning was used as a tool to show that the bi-directional communication between the CNS and the immune system does take place. We found that beta-endorphin but not dynorphin could stimulate NK cell activity, when beta-endorphin or dynorphin was injected into the CM. In addition, when anti-beta-endorphin or anti-dynorphin antibody was injected into the conditioned animals via CM the conditioned response was blocked by anti-beta-endorphin but not by anti-dynorphin antibody. These observations suggest that beta-endorphin appears to be one of the signals that is induced in the brain at the CS recall step of the conditioned response to trigger the elevation of NK cell activity.