Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. 1985.
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Animals↗
Biomedical subjects
J T Clark
Publications and source records attributed to J T Clark.
Central propranolol and pindolol, but not atenolol nor metoprolol, inhibit sexual behavior in male rats.
Are the anti-sexual effects of propranolol and pindolol due to actions within the brain? To answer this, these agents were administered directly into the brain ventricular system (ICV). Additionally, atenolol and metoprolol were evaluated to see whether differential delivery to the brain contributed to the observed lack of effect of systemically administered beta 1-adrenoceptor antagonists. ICV administration of pindolol (45 or 90 micrograms) was followed by a suppression of copulation. At 45 micrograms, inhibition was limited to performance aspects of copulation, whereas at 90 micrograms, decrements in motivational and performance aspects of copulation were evident. ICV administration of propranolol also suppressed copulatory behavior. At 45 micrograms, no significant effects were observed, whereas at 90 micrograms decrements in motivational and performance aspects of copulation were evident. In contrast, ICV administration of the beta 1-adrenoceptor antagonists, atenolol and metoprolol, was not associated with any major modifications in copulatory behavior. We suggest that the inhibitory effects of propranolol and pindolol may involve interactions with 5-HT1A receptors in the CNS. Alternatively, it may be that the adverse effects of pindolol and propranolol are due to the simultaneous blockade of both beta 1- and beta 2-adrenoceptors.
Adrenergic beta-Antagonists↗
The inhibitory effects of propranolol on genital reflexes in male rats.
We have previously reported that propranolol adversely affects sexual behavior in male rats. To elucidate whether the effects of propranolol might involve decrements in ability, we examined two components of sexual function ex copula--ejaculatory reflex capacity and erectile reflexes. In the first study, we examined the effects of various doses of (+/-)-propranolol (1.25-10 mg/kg) administered subcutaneously. Marked inhibition was observed, evidenced by increases in the latency to ex copula ejaculation and to initial erection and decrements in the number of seminal emissions and in the number of erectile reflexes. Analyses of dose-response relationships indicated that the degree of inhibition increased with increasing dose. In the second study, we evaluated the stereo-selectivity of the responses. Both (+)- and (-)-propranolol (1.25 mg/kg) significantly inhibited ejaculatory reflex potential, and although (+)- and (-)-propranolol significantly inhibited erectile reflexes, (-)-propranolol had a greater effect. The data are interpreted to indicate that a) propranolol-induced sexual dysfunction involves both motivational and ability aspects; and b) propranolol-induced inhibition of genital reflexes may be due, at least in part, to mechanisms other than beta-adrenoceptor blockade.
Adrenergic beta-Antagonists↗
Testosterone-induced copulatory behavior is affected by the postcastration interval.
A well entrenched hypothesis regarding hormonal action is that as the time interval following hormonal deprivation increases there is a corresponding decrease in the sensitivity of the system to the effects of hormone replacement. With this in mind, we examined the effects of a prolonged period of hormonal deprivation (9 mo), and compared these to the effects of a shorter period (1 month), on the restoration of copulatory behavior and seminal vesicle weights. Castration of sexually vigorous male Long-Evans rats at 6 mo of age was followed by the virtual disappearance of ejaculatory behavior within 1 mo. Testosterone (T) was administered (5 mm or 20 mm T-containing Silastic capsules) either 1 or 9 mo after castration, and copulatory tests were conducted 3, 7, 10, 14, and 17 days later. 5 mmT and 20 mmT were equally effective in restoring behavior in the rats treated 1 mo after castration. In contrast, 5 mmT was more effective in inducing copulatory behavior than 20 mmT in the rats treated 9 mo after castration. The time course to maximal effect was longer in the rats given T 9 mo after castration. Rats were sacrificed 21 days after T administration. Expressed seminal vesicle weights and plasma testosterone were increased in a dose-dependent manner independent of the postcastration interval. These data indicate that somatic and behavioral effects of T are differentially modified by the period of preceding hormonal deprivation.
Aging↗
Sexual function in altered physiological states: comparison of effects of hypertension, diabetes, hyperprolactinemia, and others to "normal" aging in male rats.
In this review, we examine the changes in sexual function that accompany deviations from "normal" physiological states. We propose that the changes one observes in many altered physiological states should not be viewed in isolation. We describe our paradigms for assessing sexual function, and proceed to evaluate how sexual function changes with hormonal deprivation and aging, in rat models for hypertension, in severe hyperprolactinemia, in streptozotocin-induced diabetes, after chronic alcohol intake, after chronic morphine administration, and after exposure to the heavy metal, cadmium. We will provide evidence for the involvement of adrenergic transmitters and two neuropeptides, neuropeptide Y and somatostatin, in the neuroendocrine regulation of sexual behavior. Finally, we compare and contrast the changes observed relative to the changes seen in "normal" aging in rats. The sequence of age-related changes in sexual function is distinct. The first change observed is a decrement in ex copula erectile reflexes. Next are decreases in ejaculatory threshold, followed shortly by increases in initiation and reinitiation of copulation after ejaculation. This is followed by a decrement in the number of males copulating to ejaculation. Finally, there is a failure to initiate the copulatory process. This sequelae is relatively common, being evident after castration, with hyperprolactinemia, and after exposure to cadmium. The data available for sexual function in hypertension is incomplete and modified by the etiology, but a suggestion for this sequelae is seen in SHR. In contrast, sexual dysfunction associated with chronic morphine administration appears to be due to an initial deficit in motivational aspects. Testosterone reverses sexual dysfunction associated with castration, but not with idiopathic sexual inactivity, nor with sexual dysfunction associated with aging, diabetes, or chronic morphine administration. Comparing sexual function in rat models for hypertension, diabetes and chronic ethanol leads to the conclusion that increases in blood pressure, like decreases in testosterone, cannot be the primary causal factor for sexual dysfunction. Age, hormonal history of the subject, and the age at castration influence changes in sexual function. Age-related sexual dysfunction appears to be contributed to by changes in adrenergic-neuropeptidergic, to include sympathetic, systems. Site-specific administration of NPY induces alterations in parameters of copulatory behavior which mimic those seen in aging and the retention of ejaculatory behavior with aging is associated with site-selective attenuation (or reversal) of age-associated changes in NPY content. Yohimbine enhances copulatory activity in castrated and aging rats, and attenuates or reverses the antisexual effects of clonidine, epinephrine and somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Cadmium-induced sexual dysfunction does not involve increased hepatic metabolism of testosterone nor increased circulating levels of corticosterone.
Sexually experienced male rats were injected IP with 0, 0.3, 1.5, 3.0, or 6.0 mg/kg cadmium chloride. The highest dose was fatal within 48 h of injection. A dose-related deficit in erectile function was observed in ex copula tests 48 h after injection. Copulatory dysfunction was evident in mating tests 72 h after injection. Hepatic mixed function oxidase activity after 0.3 mg/kg injections was not different from controls, but was diminished by 50% in rats treated with 3.0 mg/kg. The higher cadmium doses (1.5 and 3.0 mg/kg) were associated with equivalent and marked reductions in circulating testosterone levels, and lesser decrements in circulating corticosterone levels. The rats treated with 1.5 or 3.0 mg/kg cadmium chloride lost weight (32 +/- 12 and 39 +/- 9 g, respectively). Relative decapsulated adrenal gland weights were markedly increased in rats treated with 3.0 mg/kg. These data indicate that exposure to cadmium is associated with alterations in sexual, hepatic, and adrenal function, with erectile dysfunction occurring at the lowest dose. The effects on copulatory behavior are especially striking because it requires some weeks for copulatory behavior to wane following castration.
Adrenal Glands↗
Hormones and sexual behavior in relationship to aging in male rats.
To determine if the age-related decline in male sex behavior is correlated with hormonal factors, a longitudinal study was conducted. Sexually experienced males were given mating tests every 2 months from 7 through 27 months of age. To study possible relationships between changes in behavior and alterations in hormone levels, blood samples were taken before and after these bimonthly tests. At 23 months, cross-sectional studies were also conducted comparing results to those obtained in 5-month-old males. Significant changes in mating behavior first appeared at 11 months; mount latency, intromission latency, ejaculation latency, postejaculatory interval, and intercopulatory interval were increased. Similarly, detectable decreases in testosterone (T) also occurred at this age. A significant decline in luteinizing hormone (LH) was not seen until 19 months. Correlational analyses revealed small (r less than or equal to -0.29) but significant negative correlations between T and parameters of mating behavior with age. When each age was examined separately, no significant correlations appeared. Plasma T was not predictive of behavioral performance. At 23 months, cross-sectional studies revealed deficits in mounting and penile reflex behavior but ejaculatory reflex capacity was unimpaired. At 28 months, males were decapitated. Only T levels showed a significant effect of age; estradiol, prolactin, and LH were unaffected when compared to 5-month-old males. The data suggest that although there are small and significant negative correlations between circulating testosterone and parameters of mating behavior with advancing age, it is unlikely that the observed decline in testosterone is the primary cause of the age-induced behavioral deficits. It is likely that the major causal factor(s) involves non-hormone-dependent changes within the CNS.
Aging↗
Benextramine, a putative neuropeptide Y receptor antagonist, attenuates the termination of receptivity.
Sexual behavior in female rats is dependent on gonadal steroids. In ovariectomized rats, progesterone treatment typically exerts a biphasic effect on copulatory behavior induced by prior treatment with estradiol. Thus, there is an initial augmentation of the facilitative effect of estradiol occurring 4-10 h after progesterone. This is followed by a profound inhibitory effect, essentially terminating receptivity. We hypothesized that the receptivity terminating effect of progesterone could be due to increased synthesis and release of neuropeptide Y in relevant brain regions. Rats were tested for female sexual behavior 4 h after progesterone (52 h postestradiol). Immediately following this test, benextramine was administered (0, 3, or 15 mg/kg, IP). Subsequently, behavioral tests were administered 24, 48, 72, and 96 h postbenextramine. Benextramine treatment attenuated the inhibitory effects of progesterone on receptivity (lordosis quotients and percent of responding animals) without affecting either proceptive or rejection behaviors. These data suggest that blockade of NPY (and alpha-adrenergic) receptors is associated with selective enhancements of specific components of sexual behavior in female rats. Specifically, blockade of NPY receptors by benextramine is associated with continued receptivity.
Adrenergic alpha-Antagonists↗
Suppression of copulatory behavior in male rats following central administration of clonidine.
Adrenergic transmitters have been implicated in the regulation of male sexual behavior. In the present study the contribution of alpha 2-adrenoceptors, located within the central nervous system, was evaluated. Sexually experienced male Long-Evans rats were implanted with a permanent cannula in either the third cerebral ventricle or, unilaterally, in the medial preoptic area. Baseline mating tests were administered 4, 7 and 10 days after surgery and only males ejaculating (at least) in the 7 and 10 day tests were used. Clonidine-evoked dose-dependent decrements in the number of males mounting, intromitting and ejaculating, with administration into the medial preoptic area more effective than into the 3rd ventricle. In those animals mating, administration of 20 nmol into the 3rd ventricle was associated with decreases in the latency to ejaculation and intercopulatory interval, whereas administration of 2 nmol into the medial preoptic area was associated with increases in these parameters and decreases in the ejaculatory threshold. Administration of yohimbine into the medial preoptic area attenuated the effects of systemically-administered clonidine and the systemic administration of yohimbine completely prevented the copulatory suppression induced by administration of clonidine into the medial preoptic area. It is suggested that central alpha 2-adrenoceptors are important in the control of male sexual behavior and that alterations in adrenergic mechanisms in the medial preoptic area may underlie sexual dysfunction of various etiologies.
Animals↗
Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum.
Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.
Amino Acid Sequence↗
Sexual function and neuropeptide Y levels in selected brain regions in male spontaneously hypertensive rats.
Sexual function was examined in spontaneously hypertensive rats (SHR) from 8 to 20 wk of age and compared with normotensive Wistar-Kyoto (WKY) and Long-Evans rats (LE). Blood pressures (evaluated indirectly) were elevated in SHR (185 +/- 2 and 195 +/- 3 mmHg at 16 and 19 wk of age, respectively) relative to WKY and LE (135-144 mmHg). SHR exhibited good copulatory behavior but displayed fewer erections (less than 20% of the number displayed by WKY or LE) in ex copula tests. At the conclusion of the study (20 wk of age), body weights were lowest in SHR, intermediate in WKY, and greatest in LE. Relative weights of testes were greater in SHR, whereas relative weights of accessory organs, pituitary and adrenal glands, and kidneys were equivalent across strains, as were circulating levels of aldosterone. Circulating levels of testosterone were higher in SHR and WKY than in LE. Neuropeptide Y (NPY) levels in the median preoptic and arcuate nuclei were significantly greater in SHR than in WKY or LE, whereas NPY levels in the medial preoptic area and the suprachiasmatic, hypothalamic dorsomedial, and hypothalamic paraventricular nuclei were equivalent in SHR and WKY, with both greater than LE. No strain differences were evident in the medial nucleus of the amygdala, the bed nucleus of the stria terminalis, the median eminence, the anterior hypothalamic nucleus, or the hypothalamic dorsomedial nucleus.
Aldosterone↗
Clonidine suppresses copulatory behavior and erectile reflexes in male rats: lack of effect of naloxone pretreatment.
Adrenergic transmitters and opioid peptides are implicated in the regulation of male sexual behavior. In the present studies we examine a possible interaction between these two neurochemical systems in the regulation of components of male sexual behavior. In mating tests, clonidine (0.25 mg/kg, 6 min pretest) induced a profound deficit in intromissive and ejaculatory behavior whereas naloxone (5 mg/kg, 20 min pretest) evinced a facilitation of ejaculatory behavior, evidenced by decreases in the ejaculation latency in the initial copulatory series and by decreases in ejaculation latency and intercopulatory interval in the second copulatory series. Importantly, prior treatment with naloxone did not prevent or attenuate the copulatory suppression induced by clonidine. In ex copula penile reflex tests, clonidine (0.25 mg/kg, 6 min pretest) decreased the incidence of seminal emission and the number of penile responses (erections, cups and flips). Naloxone (5 mg/kg, 20 min pretest) was without effect on any of the parameters of penile reflex activity and, further, failed to prevent or attenuate the erectile suppression induced by clonidine. A final study evaluated the dose-response relationship of clonidine-induced erectile dysfunction. A similar degree of erectile dysfunction was observed after 0.005, 0.025 or 0.25 mg/kg clonidine, whereas 0.0005 mg/kg was without effect. Previous studies demonstrated a dose-dependent inhibition of mounting, intromissive and ejaculatory behavior, with 0.25 mg/kg selectively eliminating ejaculatory behavior in mating tests. These data demonstrate a dose-dependent inhibition of penile reflexes, with inhibition occurring at doses lower than those required to induce copulatory dysfunction. Further, we suggest that opioid receptors sensitive to naloxone blockade are not involved in the clonidine-induced suppression of copulatory or erectile function.
Animals↗
Steroid sulfatase activity in the skin of the external ear canal.
Steroid sulfatase is an enzyme which has an important role in the complex process of cell desquamation. The specific activity of this enzyme was found to be higher in the epithelium of the deep external auditory canal than in the epithelium of the superficial external canal. We speculate that this steroid sulfatase activity gradient is involved in the outward migration of the keratinocytes of the canal epithelium.
Analysis of Variance↗
46-53 kilodalton glycoprotein from the surface of Plasmodium falciparum merozoites.
A 46-53 kDa glycoprotein antigen of Plasmodium falciparum merozoites has been identified using a murine monoclonal antibody that inhibits infection of human erythrocytes in vitro. Immunofluorescence screening with the antibody of greater than 250 isolates of the parasite finds the inhibitory epitope expressed by only 18% of strains. The glycoprotein is metabolically labelled with methionine, cysteine, histidine and glucosamine but incorporates little lysine or leucine. It is synthesized early in schizogony and remains, without any apparent processing, on the surface of released merozoites where it is demonstrated by immuno-electronmicroscopy and also by vectorial radio-iodination.
Animals↗
A possible role for angiotensin II in the regulation of male sexual behavior in rats.
To investigate the possibility that angiotensin II (AII) is involved in the regulation of male sexual behavior, AII was injected intraventricularly into sexually experienced male rats immediately prior to mating tests. Third ventricular administration of 0.48 nmol AII resulted in an increased latency to the initiation of copulatory behavior (625% of control values), and administration of 4.8 nmol had a similar effect on initiation latencies (650% of control values) and, additionally, significantly increased the number of intromissions preceding ejaculation (the ejaculatory threshold, to 130% of control values) and the interval to reinitiate copulatory behavior after ejaculation (the postejaculatory interval, to 125% of control values). Water intake was affected only by the higher dose of AII, with no animals drinking in the 15 minutes following saline or 0.48 nmol AII and 69% of the rats treated with 4.8 nmol AII drinking (mean intake 1.5 +/- 0.26 ml for those rats drinking). These data demonstrate that AII can suppress male sexual behavior, and that this suppression is not due simply to a stimulation of drinking.
Angiotensin II↗
Polymorphism of a 35-48 kDa Plasmodium falciparum merozoite surface antigen.
Glycoproteins of the asexual blood stages of Plasmodium falciparum were labelled with radioactive glucosamine and analysed by two-dimensional electrophoresis. Four major glycoproteins were detected in all eight parasite isolates studied. Two of the glycoproteins, designated GP2 and GP4, were invariant among the isolates, while the other two GP1 and GP3 were found to be polymorphic in both their biochemical and antigenic properties. By immunoblotting and immunoprecipitation with specific monoclonal antibodies, the two polymorphic glycoproteins were identified as surface antigens of merozoites.
Animals↗
Chronic morphine and testosterone treatment: effects on norepinephrine and serotonin metabolism and gonadotropin secretion in male rats.
The effects of sustained-release implants of morphine (M) and/or testosterone (T) on serum gonadotropin levels and norepinephrine (NE) and serotonin (5-HT) metabolism in brain regions were examined. While 4 days of M or 5 mm [corrected] T treatment were without significant effect, the combination dramatically decreased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Castration increased NE content of the mediobasal hypothalamus (MBH), and although M, 5 mm [corrected] T, or their combination significantly reduced NE levels in the MBH, they remained elevated compared to intact or 30 mm [corrected] T-treated rats. Further, in the MBH no differences in normetanephrine (NME) levels, nor in NME:NE ratios, nor 5-HT metabolism were evident. In the preoptic area-anterior hypothalamus, NE or 5-HT metabolism were not altered by castration and M and/or T. These results show that M and T interact to suppress LH and FSH release in the apparent absence of any appreciable effect on hypothalamic monoamines.
Animals↗
Control of feeding and sexual behaviors by neuropeptide Y: physiological implications.
Recent evidence suggests that a variety of hypothalamic neuropeptides may mediate interneuronal communication to coordinate diverse neuroendocrine and behavioral functions. In this work, we describe the effects of neuropeptide Y (NPY) on feeding and sexual behaviors. We observed that central administration of bolus NPY stimulated a robust, dose-related feeding response in satiated male and female rats. Continuous NPY receptor activation also evoked dose-related, intermittent feeding in a manner normally observed during nocturnal feeding. It appears that the paraventricular nucleus in the hypothalamus may be the primary site of NPY action because the anticipated reciprocal changes in NPY concentrations, in response to food deprivation followed by ad libitum food intake, occurred only in this site. Additional findings revealed that NPY-induced feeding may follow either substantial reduction or complete restraint of an inhibitory influence on feeding mediated by alpha 2-adrenoreceptor systems in satiated rats. Further, NPY was found to suppress male and female sexual behaviors. The suppressive effects on sexual behavior were apparent prior to or at the time of the onset of feeding after NPY administration. These observations may provide a neurochemical basis for clinical and animal studies on disorders of feeding associated with diminished reproductive functions.
Animals↗