Adult Male Monkeys Research Articles

Collection and evaluation of semen from captive howler monkeys ( Alouatta caraya)

Semen samples ( n=58) were collected by eletroejaculation from nine adult male howler monkeys ( Alouatta caraya) between November 2000 and August 2001 at the National Primates Center, Ananindeua, Brazil. The ejaculates were free of coagulum. Mean (±S.D.) values were: volume, 0.09±0.05 ml; pH, 8.1±0.5; concentration 649.5±926.7×10 6 sperm/ml; progressive motility, 75.7±18.1%; forward progressive sperm motility (scale, 0–5), 3.6±1.0; live spermatozoa, 68.3±15.0%; primary defects, 9.6±4.5%; and secondary defects, 11.8±4.6%. There were high correlations between motility and live sperm ( r=0.91, P<0.01), motility and forward progressive sperm motility ( r=0.84, P<0.01) and between forward progressive sperm motility and live sperm ( r=0.78, P<0.01). There were no alterations observed during clinical examinations and hematological analysis performed before and after semen collection. Therefore, the method was considered safe and efficient. It can be used for the evaluation of the breeding potential of male howler monkeys in captivity and for the establishment of new assisted reproductive technology (ART) for threatened species of neotropical primates.

Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones

Estrogen produced by aromatization of gonadal androgen has an important facilitative role in male-typical aggressive behavior that is mediated through its interaction with estrogen receptors (ER) in the brain. Isoflavones found in soybeans and soy-based dietary supplements bind ER and have dose- and tissue-dependent effects on estrogen-mediated responses. Yet, effects of isoflavone-rich diets on social and aggressive behavior have not been studied. We studied the effects of long-term (15 months) consumption of diets rich in soy isoflavones on spontaneous social behavior among adult male cynomolgus macaques ( Macaca fascicularis) ( n = 44) living in nine stable social groups. There were three experimental conditions which differed only by the source of dietary protein: casein and lactalbumin (no isoflavones), soy protein isolate containing 0.94 mg isoflavones/g protein, and soy protein isolate containing 1.88 mg isoflavones/g protein. In the monkeys fed the higher amount of isoflavones, frequencies of intense aggressive (67% higher) and submissive (203% higher) behavior were elevated relative to monkeys fed the control diet ( P's < 0.05). In addition, the proportion of time spent by these monkeys in physical contact with other monkeys was reduced by 68%, time spent in proximity to other monkeys was reduced 50%, and time spent alone was increased 30% ( P's < 0.02). There were no effects of treatment on serum testosterone or estradiol concentrations or the response of plasma testosterone to exogenous gonadotropin-releasing hormone (GnRH). The results indicate that long-term consumption of a diet rich in soy isoflavones can have marked influences on patterns of aggressive and social behavior.

Cryopreservation of Sperm of an Endangered Species— Assamese Macaque

The Assamese macaque (Macaca assamensis) is a rare and endangered species, which can only be found now in northern India and southwest China. There is an urgent need to cryopreserve Assamese macaque sperm for the conservation of this endangered species. Spermatozoa were collected from four adult male monkeys (Assamese macaque) using penile electroejaculation. In the light of the previous research on cryopreservation of cynomolgus macaque and rhesus monkey sperm, we developed an effective technique for cryopreservation of Assamese macaque sperm using TTE (TES + Tris + egg yolk) as an extender (base solution) with 5% (vol/vol) glycerol (as a cryoprotectant). Sperm motility and sperm penetration rate of zona-free hamster oocytes were measured to evaluate post-thawed sperm viability and function. In comparison with fresh sperm, the post-thawed sperm motility right after thawing was 69 ± 5% (n = 9). After incubation for 1, 2, 4, 6, 8, and 10 h, post-thawed sperm motility was 60.6 ± 2.1, 37.9 ± 12.4, 31.4 ± 14....

Endothelial dysfunction in a primate model of cerebral vasospasm.

Although abnormalities in the control of endothelial vasomotility have been reported in both experimental and clinical studies, the mechanism of the endothelial dysfunction that occurs following subarachnoid hemorrhage (SAH) remains unclear. Because of the absence of previous in vivo studies of endothelial function in cerebral vessels in response to SAH or cerebral vasospasm, the authors investigated endothelium-dependent responses in an established primate model of vasospasm after SAH. Endothelial function was assessed by examining vascular responses to intracarotid injections of various drugs known to act via the endothelium. Drugs that have a rapid total body clearance were selected so that their pharmacological effects would be limited to the cerebral circulation after an intracarotid infusion. Seventeen adult male cynomolgus monkeys were used. Cerebrovascular endothelium-dependent responses were examined in control animals and in animals with SAH 7, 14, and 21 days after placement of a subarachnoid clot around the right middle cerebral artery. Cortical cerebral blood flow (CBF) and cerebrovascular resistance (CVR) were recorded continuously during 5-minute intracarotid infusions of 5% dextrose vehicle, acetylcholine, histamine, bradykinin, or Calcimycin. In control animals the intracarotid infusion of acetylcholine produced a significant (7.8 +/- 9.5%) increase in CBF and a 9.3 +/- 8.7% reduction in CVR in comparison with a control infusion of dextrose vehicle. The responses to acetylcholine disappeared in animals 7 days post-SAH, specifically in the subset of animals in which arteriography confirmed the presence of vasospasm. Infusion of Calcimycin produced no significant changes in CBF or CVR in control animals, but resulted in a significant reduction in CBF and increase in CVR in animals 7 days after SAH and in animals with vasospasm. An infusion of histamine or bradykinin had no significant effect on CBF or CVR. An intracarotid infusion of acetylcholine, but not one of histamine, bradykinin, or Calcimycin, produced a measurable physiological response in the normal primate cerebrovasculature. Cerebral vasospasm that occurred after SAH produced a pathophysiological effect similar to the endothelial denudation shown in the in vitro experiments of Furchgott and Zawadzki, in which acetylcholine constricted the vessels via activation of receptors on smooth-muscle cells. Changes in vascular responses to acetylcholine and Calcimycin in animals with vasospasm, compared with control animals, provide evidence that endothelial dysfunction plays a key role in the development and/or sustenance of vasospasm after SAH.

Induction of infertility in adult male bonnet monkeys by immunization with phage-expressed peptides of the extracellular domain of FSH receptor

Active immunization of proven fertile adult male bonnet monkeys ( Macaca radiata) with phage-expressed follicle-stimulating hormone receptor (FSHR)-specific peptides from the extracellular domain resulted in a progressive drop in sperm count with all animals becoming azoospermic by day 100. However, serum testosterone concentrations were unaltered during the entire course of study and animals exhibited normal mating behaviour. Breeding studies with proven fertile female monkeys revealed that all the immunized males were infertile. Following interruption of immunization on day 225, sperm counts returned to normal with restoration of fertility. These results indicate that infertility can be induced in adult male monkeys by interfering with the action of FSH using specific peptides of the extracellular domain of FSHR as antigens, without the risk of producing cross-reacting antibodies to the other glycoprotein hormones.

Intérêts et limites de l’immunocontraception

Recent studies from WHO indicated that a large proportion of human contraceptive needs cannot be covered by the already existing means for different reasons (medical, economical, political, and cultural). Therefore, development of new effective methods targeting birth control methods affordable by under-privileged populations turns out to be necessary. Over the last 20 years, a large number of strategies have been used for contraceptive vaccines and thus multiple antigens have been identified as potential targets for immunocontraception. Nowadays, the most acute researches are based on suppression of the secretion and the activity of gonadotropic hormones (GnRH, LH/hCG, FSH) or the targeting of antibodies specific to sperm surface (RSA-1, SP10, SP17, TCLe-1, PH-20) and oocyte antigens (ZP1, ZP2, ZP3). We developed a contraceptive vaccine against FSH receptor. Adult male monkeys ( Macaca radiata) were immunized with filamentous phages displaying at their surface N-terminal peptides of the FSH receptor. Long term male contraception has been achieved without any alteration of circulating testosterone levels, sexual behaviour or of any other discernable metabolic changes. Interruption of vaccination resulted in full recovery of sperm production and male fertility. Contraceptive vaccines are aimed to block an essential step in the reproductive process. From this point of view, efforts have to be focused on the challenge to raise is to ally our knowledge on reproductive physiology and protein biochemistry for a better understanding of the target antigen’s function.

Circadian Determinations of Cortisol, Prolactin and Melatonin in Chronic Methyl-Phenyl-Tetrahydropyridine-Treated Monkeys

The aim of this study was to investigate whether prolactin, melatonin and cortisol are altered in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and if so, whether MPTP may alter the availability of these hormones in chronic experimental parkinsonism. Furthermore, vegetative and sleep disorders have been described in both parkinsonian patients and in MPTP chronic monkeys; these may result indirectly from concomitant hormonal variations. Seven adult male cynomolgus monkeys were used for this experiment. Five were treated with systemic doses of intravenous MPTP but not with L-DOPA or dopaminergic agonists. In their 3rd year of parkinsonism, plasma samples were obtained day and night at 3-hour intervals. Sample collection was repeated three times for each animal. Prolactin, melatonin and cortisol concentrations were determined by enzyme immunoassay and compared with samples taken from the control group. Both MPTP-treated monkeys and the control group displayed a similar secretion pattern for the three hormones, except at several specific times when prolactin and melatonin showed significant differences. No changes were found for cortisol. The results suggest a possible alteration of hormonal metabolism in chronic MPTP parkinsonian monkeys.

Prevention of cerebral vasospasm by a humanized anti-CD11/CD18 monoclonal antibody administered after experimental subarachnoid hemorrhage in nonhuman primates.

Leukocyte-endothelial cell interactions occurring in the first hours after subarachnoid hemorrhage (SAH) initiate changes in the endothelium and vessel wall that lead to an influx of leukocytes and the development of chronic vasospasm days later. Upregulation of intercellular adhesion molecule-1 (ICAM-1), also called CD54, appears to be a crucial step in this process. There is increasing experimental evidence that blocking the interaction between ICAM-1, which is expressed on endothelium, and integrins such as lymphocyte function-associated antigen-1 (CD11a/CD18) and macrophage antigen-1 (complement receptor 3, CD11b/CD18), which are expressed on the surface of leukocytes,prevents not only inflammation of vessel walls but also chronic vasospasm. The authors extend their previous work with monoclonal antibody (mAb) blockade of leukocyte migration to a nonhuman primate model of chronic, posthemorrhagic cerebral vasospasm. Before surgery was performed, six young adult male cynomolgus monkeys underwent baseline selective biplane common carotid and vertebrobasilar artery cerebral angiography via a transfemoral route. On Day 0, a right frontosphenotemporal craniectomy was performed with arachnoid microdissection and placement of 2 to 3 ml of clotted autologous blood in the ipsilateral basal cisterns. The animals were given daily intravenous infusions of 2 mg/kg of either a humanized anti-CD11/CD18 or a placebo mAb beginning 30 to 60 minutes postoperatively. The monkeys were killed on Day 7 after a repeated selective cerebral angiogram was obtained. The area of contrast-containing vessels observed in each hemisphere on anteroposterior angiographic views was calculated for the angiograms obtained on Day 7 and expressed as a percentage of the area on baseline angiograms (percent control areal fraction). Review of flow cytometry and enzyme immunoassay data confirmed the presence of the anti-CD11/CD18 antibody in the serum and bound to leukocytes in the peripheral blood of treated animals. Comparisons of the groups revealed 53 +/- 4.8% control vascular areal fraction in the placebo group (two animals) and 95.8 +/- 9.4% in the anti-CD11/CD18-treated group (three animals), a statistically significant difference (p = 0.043, t-test). These results show that blockade of leukocyte migration into the subarachnoid space by an anti-CD11/CD18 mAb is effective in preventing experimental cerebral vasospasm in nonhuman primates, despite the unaltered presence of hemoglobin in the subarachnoid space. These experimental data support the hypothesis that inflammation plays a role in cerebral vasospasm after SAH.

Morphometry and histochemistry of the semitendinosus muscle of tufted capuchin monkeys (Cebus apella Linnaeus, 1758).

Considering monkeys are animals closely related to the human, and semitendinosus muscle has been used in many postural research experiments, we have decided to study its histochemical characteristics. Samples were removed from the proximal, middle and distal regions of the semitendinosus muscles of five adult male tufted capuchin monkeys and observed for reaction with m-ATPase (with alkaline and acid pre-incubation), nicotinamide adenine dinucleotide tetrazolium reductase, and haematoxylin and eosin. The muscle fibres were classified as fast glycolytic (FG), fast oxidative glycolytic (FOG) and slow oxidative (SO) and quantified in terms of frequency and area. The three regions of the semitendinosus muscle showed no significant differences in frequency or area of the respective fibre types, and therefore the muscle can be considered histoenzymologically homogeneous. FG fibres presented higher frequencies and larger areas. The sum of FOG and SO fibres was 57.5%, suggesting that the semitendinosus muscle of the tufted capuchin monkey is adapted to an action involved in posture maintenance and in long arboreal dislocation. The present data agrees with the notion of differentiated quadrupedalism in some primates, which support a lower percentage of their weight on the fore limbs.

Noninvasive technique for the repeated sampling of salivary free cortisol in awake, unrestrained squirrel monkeys.

The use of noninvasive measures of hypothalamic-pituitary-adrenal (HPA) axis function is of growing interest among preclinical and clinical investigators. This report describes a method for the repeated assessment of salivary free cortisol in awake, unrestrained squirrel monkeys (Saimiri sciureus) based on a saliva sampling technique previously developed for rhesus monkeys. Individually housed adult male squirrel monkeys were trained to chew on dental rope attached to a pole, from which saliva was extracted by centrifugation and analyzed for cortisol by radioimmunoassay (RIA). Eight of nine monkeys readily acquired the task, reliably providing adequate saliva samples for the assay. Salivary free cortisol levels were examined in these subjects under basal conditions and in response to two types of neuroendocrine challenge. Levels of salivary free cortisol showed relatively low intra- and interindividual variability, with mean individual morning levels ranging between 17.1 and 37.9 microg/dl. Squirrel monkeys demonstrated a consistent daily rhythm in salivary free cortisol ranging from a high of 27.4 +/- 5.2 microg/dl (mean +/- SEM) at 12 P.M. to a low of 7.5 +/- 1.6 microg/dl at 6 P.M. Intravenous (IV) challenges with 1 microg/kg ACTH, or 10 and 50 microg/kg CRF resulted in significant increases in salivary free cortisol. The described sampling technique provides a reliable and sensitive means for repeated measurement of HPA activity in unrestrained, awake squirrel monkeys. In addition, our findings illustrate several features of HPA system rhythmicity and reactivity using salivary cortisol instead of blood plasma or serum.

Effect of oral tamoxifen on semen characteristics and serum hormone profile in male bonnet monkeys

The effects of oral tamoxifen were studied at a dose of 0.4 mg/kg per day, on the serum hormones and semen parameters in adult male bonnet monkeys, for a period of 90 days. Honey was used as vehicle. Monkeys were treated with honey for 30 days, followed by tamoxifen from Day 30–120 (90 days). Thereafter the treatment was withdrawn until Day 150 of schedule. Blood samples were drawn at 12 and 24 clock hours at monthly intervals for the analysis of luteinizing hormone, follicle-stimulating hormone and testosterone. Semen samples were also collected for analysis once a month, from Day 0–150 of exposure. Tamoxifen treatment produced a transient but significant increase in circulating gonadotropins, at Day 90 of treatment schedule, corresponding to 60 days of treatment. Whilst serum testosterone levels were normal throughout treatment period, an increase was observed after 30 days of drug withdrawal. No effect of oral tamoxifen was evident on semen parameters, viz., volume, counts, morphology and motility. However, throughout the exposure period to honey, a significant increase was observed in sperm counts without any effect on testosterone levels. The present study suggests that oral tamoxifen has a transient antiestrogenic effect on the serum hormones and no effect on semen parameters of adult nonhuman primate males. It is concluded that bioefficacy of oral tamoxifen may have been reduced due to hepatic metabolism.

Inhibitory and stimulatory regulation of testicular inhibin B secretion by luteinizing hormone and follicle-stimulating hormone, respectively, in the rhesus monkey (Macaca mulatta).

This study examined the relative role of FSH and LH in governing testicular inhibin B secretion in the rhesus monkey. Adult male monkeys, rendered hypogonadotropic and hypogonadal by administration of a GnRH receptor antagonist (acyline), were implanted with testosterone (T)-filled or empty capsules. Following T-induced restoration of spermatogenesis, both groups received recombinant human FSH and vehicle for 12 d. Juvenile male monkeys received an 11-d infusion of single-chain recombinant human LH and recombinant human FSH, either alone or in combination. In adults, chronic hypogonadotropism resulted in a modest reduction of circulating inhibin B levels, which was more than fully reversed by FSH. In the presence of T, which exerted a marked suppression in inhibin B secretion, FSH restored inhibin B levels only to those observed before acyline treatment. In juveniles, treatment with single-chain recombinant human LH led to a suppression of inhibin B secretion and curtailed the FSH-induced stimulation of this testicular hormone. The T-induced decrease in inhibin B secretion was associated with suppression in inhibin-beta(B) mRNA levels, but FSH stimulation of inhibin B secretion occurred in the absence of clear changes in expression of this subunit gene. These findings indicate that inhibin B secretion by the monkey testis is governed by the inhibitory and stimulatory action of LH and FSH, respectively. The action of LH is presumably indirect and likely mediated by T inhibition of inhibin-beta(B) gene expression. The molecular basis of the stimulatory action of FSH on inhibin B secretion requires further study.

Androgen receptors in gonadotrophs in pituitary cultures from adult male monkeys and rats.

There is substantial evidence demonstrating that the principal feedback action of androgens to decrease LH secretion in male primates, including man, is to slow the GnRH pulse generator, whereas in male rats androgens not only decrease GnRH but also suppress LH synthesis and secretion through a direct pituitary effect. Previous experiments in our laboratory revealed that testosterone (T) suppresses LH secretion and decreases alpha-subunit mRNA levels in male rat pituitary cell cultures perifused with pulses of GnRH but not in pituitary cells from adult male monkeys. In the present study, we sought to determine whether the lack of responsiveness of gonadotrophs to androgens in the primate is androgen receptor (AR) related. Primary cultures were prepared from the anterior pituitary glands of adult male monkeys and rats. Cells were identified as gonadotrophs if they were immunoreactive for LH-beta or FSH-beta. Of these cells in the monkey, 80% contained both gonadotropins, 17% contained only LH-beta, and 3% contained only FSH-beta. AR immunoreactivity (IR) was nuclear in 22% and 15%, respectively, of monkey and rat FSH-beta-positive cells in the absence of T. Following T treatment, nuclear AR IR was identified in 79% of monkey and 81% of rat gonadotrophs. T treatment similarly intensified AR IR in mouse gonadotroph alphaT3-1 and LbetaT2 cells and in monkey and rat fibroblasts. Single-cell RT-PCR confirmed coexpression of LH-beta and AR mRNA as well as LH-beta and GH mRNA in monkey gonadotrophs. Our data reveal that most monkey, as well as rat, gonadotrophs are AR-positive with nuclear localization in the presence of T. GH expression is not required for AR expression in gonadotrophs. We conclude that the failure of T to inhibit LH secretion and decrease alpha-subunit mRNA expression in the male primate is not due a disturbance in AR nuclear shuttling.

Effect of chronic administration of 7alpha-methyl-19-nortestosterone on serum testosterone, number of spermatozoa and fertility in adult male bonnet monkeys (Macaca radiata).

Hormonal approaches to male contraception that are based on the suppression of LH secretion require androgen replacement treatment to maintain sexual behaviour and secondary sexual characteristics. Androgen supplementation not only involves large and frequent doses of testosterone esters but also results in undesirable effects on the prostate gland. In an attempt to avoid such problems, a synthetic androgen, 7alpha-methyl-19-nortestosterone (MENT), which is much more potent than testosterone, has been developed. In the present study, MENT was administered at different doses (25, 50, 100, 300 and 1000 microg day(-1)) either alone or in combination with oestradiol via Silastic implants for a specified period to adult male bonnet monkeys (Macaca radiata). Blood and semen samples were collected at specific intervals and analysed for serum testosterone and seminal parameters, respectively. The results of the present study clearly indicate that administration of MENT at all doses tested results in suppression of the nocturnal surge of testosterone (by day 3), as well as a decrease in the number of spermatozoa (by day 45). Co-administration of oestradiol resulted in a reduction in the dose of MENT required to suppress the nocturnal surge. None of the male bonnet monkeys treated with MENT were able to impregnate females, clearly demonstrating the efficacy of MENT in blocking fertility in male bonnet monkeys.

Effect of chronic administration of 7alpha-methyl-19-nortestosterone on serum testosterone, number of spermatozoa and fertility in adult male bonnet monkeys (Macaca radiata)

Effect of chronic administration of 7alpha-methyl-19-nortestosterone on serum testosterone, number of spermatozoa and fertility in adult male bonnet monkeys (Macaca radiata)

Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol.

Some of the statin-induced reduction in cardiac events in patients with atherosclerosis may be derived from mechanisms independent of lipid lowering. This study tested in nonhuman primates whether statins can influence inflammation (indicated by vascular cell adhesion molecule-1, interleukin-1beta, tissue factor, and macrophages) and features of plaque stability (indicated by collagen and smooth muscle cells) independent of their effect on plasma cholesterol level. Adult male cynomolgus monkeys (n=12 per group) consumed an atherogenic diet for 12 months while receiving (1) no treatment (control), (2) pravastatin (Prava, 40 mg/kg per day), or (3) simvastatin (Simva, 20 mg/kg per day). Dietary cholesterol was adjusted to equalize plasma cholesterol levels among groups. Although the intima/media ratio in the abdominal aorta did not differ among groups, drug treatment reduced inflammation and features of plaque vulnerability. Macrophage content in the lesions of statin-treated animals was lowered (2.4-fold with Prava and 1.3-fold with Simva; both P<0.001 versus control). Furthermore, lesions had approximately 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression in statin-treated versus control animals (P<0.005). Lesional smooth muscle cell and collagen content was 2.1-fold greater in the Prava-treated group (P<0.001) and 1.5-fold greater in the Simva-treated group (P<0.005) than in the control group. In primates, these results provide further support for the beneficial effect of statins on plaque inflammation and stability in addition to cholesterol lowering.

Intracytoplasmic injection of frozen-thawed epididymal spermatozoa in a nonhuman primate model, the cynomolgus monkey ( Macaca fascicularis)

Intracytoplasmic sperm injection (ICSI) with frozen-thawed epididymal spermatozoa was performed in the cynomolgus monkey ( Macaca fascicularis) to produce embryos in vitro. Eleven sexually mature females were hyperstimulated with an GnRH agonist (1.8 mg active triptorelin per 2 kg body weight), followed (2 weeks later) by rFSH (37.5 IU per 2 kg daily) for 12 days, and finally 1000 IU of hCG. Epididymal spermatozoa were collected from a single adult male monkey. The first stimulation cycle resulted in 90 oocytes; 70% of which were metaphase II (MII). Sixty-four percent of these MII oocytes were fertilized. Comparing ovarian response of five monkeys that underwent a second stimulation cycle there was an increase in oocyte quantity (13.2 versus 9.2 oocytes per monkey) but the percentage of MII oocytes remained the same at 58%. Fertilization and cleavage rates were also reduced but there was an increase in the number of embryos available for transfer. Overall, four monkeys became pregnant resulting in the birth of two healthy infants and two abortions. These findings show that [1] ovarian stimulation by GnRH–rFSH did not compromise the developmental competence of the oocytes; [2] effective combination of cryopreservation of epididymal spermatozoa and ICSI is possible in nonhuman primate reproduction, and thus has potential application in the conservation of highly endangered nonhuman primate species, and [3] the cynomolgus monkey is a reliable biomedical research model to study the potential risks and benefits associated with assisted reproductive techniques prior to approval for clinical trials on humans.

Variability in sperm suppression during testosterone administration to adult monkeys is related to follicle stimulating hormone suppression and not to intratesticular androgens.

Sex steroid-based male contraceptive regimens do not induce consistent azoospermia. The reason for this variable response is obscure. We used normal adult male monkeys, Macaca fascicularis (n = 9) as a model of testosterone (T)-induced gonadotropin suppression to understand the basis for variability in spermatogenic suppression during hormonal contraception. As observed in men, T administration to these monkeys induced azoospermia in some animals and variable degrees of spermatogenic suppression in others. Based on their sperm counts, we divided these animals into two groups: azoospermic (azoo; n = 4) and nonazoospermic (nonazoo; n = 5) groups. Sperm density, testis volumes, and serum T, bioassayable LH (bioLH), immunoassayable FSH (immunoFSH), bioassayable FSH (bioFSH), and inhibin B were examined every 2 wk during the control period, 20 wk of T administration using SILASTIC brand (Dow Corning Corp.) implants, and recovery. Testes were biopsied for estimation of intratesticular T, dihydrotestosterone, and 5alpha-androstane-3alpha,17beta-diol. Serum T levels increased 1.5- to 2-fold, leading to decreased bioLH levels (48% of control) and intratesticular T levels (15% of control); neither LH nor intratesticular T levels differed between the azoo and nonazoo groups. In contrast, serum levels of FSH, by both bio- and immunoassay, during T administration were significantly lower in the azoo than in the nonazoo group. These results suggest that the degree of suppression of spermatogenesis is closely related to the degree of suppression of FSH levels and not to the levels of intratesticular androgens or to serum LH. These results imply that FSH plays a key role in supporting spermatogenesis in monkeys in this experimental regimen and suggest that maximal suppression of FSH may be essential to ensure consistent azoospermia in men during hormonal contraception.

The finding of an inverse relationship between social dominance and feeding priority among pairs of unfamiliar adult male vervet monkeys (Cercopithecus aethiops sabaeus).

Dominance is often presumed to confer priority of access to resources. This study evaluated the relationship between two assessments of dominance: (1) social dominance, based on agonistic interactions and (2) feeding priority among pairs of unfamiliar adult vervet monkeys (Cercopithecus aethiops sabaeus) differing in scrotal colour, but matched for height, weight and testicular volume, during paired introduction experiments. Results of this investigation showed that neither size differences nor scrotal colour were predictive of feeding priority, and social dominance was inversely related to feeding priority. This finding demonstrates that different assessments of dominance can yield different outcomes even within the same primate taxon. I propose that male dominance rank may best predict access to resources when there is direct contest competition over a resource, which is not immediately exhaustible, whereas highly impulsive low ranking males may gain a competitive edge in scramble competitions for ephemeral and small resources.

Characterization of the discriminative stimulus effects of N-methyl- D-aspartate ligands under different ethanol training conditions in the cynomolgus monkey ( Macaca fascicularis).

The current study was designed to extend our knowledge of the N-methyl- D-aspartate (NMDA) glutamate receptor system in mediating the discriminative stimulus effects of ethanol in non-human primates. To characterize the discriminative stimulus effects of the NMDA uncompetitive antagonists dizocilpine, phencyclidine (PCP) and ketamine in male and female monkeys under different ethanol training conditions. Adult male ( n=8) and female ( n=9) cynomolgus monkeys ( Macaca fascicularis) were divided into four groups and trained to discriminate 1.0 g/kg ethanol ( n=8) versus water or 2.0 g/kg ethanol ( n=9) versus water in a 2 x 2 design with training dose and sex as main group factors. Ethanol (20% w/v) solutions were administered intragastrically (IG) and responding was maintained under a fixed ratio schedule of food reinforcement. Dose-response determinations for dizocilpine [IG and intramuscular (IM)], PCP (IM) and ketamine (IM) were made under two training intervals (30 and 60 min). Dizocilpine, PCP and ketamine dose-dependently substituted for ethanol in three of four training conditions, the notable exception being in males trained with 2.0 g/kg ethanol. Ethanol-like discriminative stimulus effects were greater with IM dizocilpine than with IG dizocilpine. At the lower ethanol training dose (1.0 g/kg), there were no sex differences in the ethanol-like discriminative stimulus effects of dizocilpine, PCP or ketamine, nor were there sex differences in the potencies to produce ethanol-like discriminative stimulus effects. Sex differences were readily apparent with the higher ethanol training dose (2.0 g/kg), with the NMDA ligands failing to substitute for ethanol in male monkeys, probably due to the rate-suppressive effects of these compounds. These data suggest that NMDA receptor-mediated activity is a component to the discriminative stimulus effects of ethanol in male and female nonhuman primates. However, NMDA uncompetitive antagonists were less likely to produce discriminative stimulus effects similar to a high ethanol training dose in male monkeys. In comparison to consistent substitution by GABA(A) positive modulators for ethanol, substitution patterns produced by NMDA uncompetitive antagonists suggest a less robust mediation of the ethanol discriminative stimulus through NMDA receptor systems in nonhuman primates.