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The effects of diethylstilbestrol (DES) before birth on the development of masculine behavior in juvenile female rhesus monkeys.

Eight pregnant rhesus monkeys were injected with 100 microg diethylstilbestrol dipropionate (DESDP) from the 40th day of gestation until term, a long-term treatment. Male (n = 3) and female (n = 5) offspring were obtained. Five other pregnant females were injected with DESDP beginning on the 115th day of gestation and continuing until either the 140th day or term--a relatively short-term treatment. Five female infants were obtained from these short-term treatments. Monkeys from the treated pregnancies were assigned randomly to mother-infant social groups containing untreated male and female infants the same age. They were observed in their peer groups each weekday from 3 to 12 months of age, and the display of mounting and play behavior was recorded for each subject. Results showed that DESDP significantly increased the frequency of display of these juvenile behaviors only in long-term-treated females. However, one of the aspects of mounting that is characteristic of males (the ratio of complete to abortive mounts) was unaffected even by the long-term treatment. Thus, DESDP-treated females displayed a limited behavioral masculinization. Whether this limitation was due to dosage and/or timing or to a selective action of DESDP was not determined. DESDP-treated males were not altered in any measurable way compared to untreated males.

Animals↗

Effect of cyproterone acetate on prolactin secretion in the female Rhesus monkey.

Adult female rhesus monkeys were given cyproterone acetate orally in doses of 0.04, 0.4, 4 and 40 mg per kg per day for 12 weeks. Its effects were assessed on serum prolactin (PRL) concentration, the morphology of the PRL cells, and the development of the mammary glands. Serum PRL was relatively unchanged in the control animals from the fourth through the twelfth weeks of the study. In contrast, PRL was significantly elevated in each group of drug-treated animals during the same time periods. There was no development of the mammary glands nor was there any evidence of milk secretion in the control animals; however, in the monkeys given cyproterone acetate the mammary glands had extensive lobuloalveolar growth and milk-like secretion that could be expressed as early as the fourth or fifth week of the study. By immunocytochemistry and differential light microscopic staining techniques, the PRL cells in the pituitary glands of the experimental animals were found to be more numerous and much larger than those present in the controls. They displayed a well developed Golgi complex and had an abundance of cytoplasmic RNA. These data suggest that PRL secretion is markedly enhanced by cyproterone acetate.

Animals↗

Organization of the thalamo-cortical connexions to the frontal lobe in the rhesus monkey.

In 25 rhesus monkeys horseradish peroxidase was injected in different parts of the frontal cortex. The retrogradely labelled thalamic neurons formed longitudinal bands, some of which crossed the internal medullary lamina, and extended from one thalamic nucleus into another. On the basis of these findings the frontal cortex was subdivided into seven transverse cortical strips which receive afferents from seven longitudinal bands of thalamic neurons. The most rostral transverse strip receives afferents from the most medial thalamic band which is oriented vertically and extends through the most medial part of the MD into the medial pulvinar. Progressively more caudally located transverse strips receive afferents from progressively more laterally located thalamic bands which in part are situated in the VL and show an increasing tilt towards the horizontal. Moreover, those parts of the various bands which are situated along the dorsal and lateral margin of the thalamus project to the medial portions of the transverse cortical strips, i.e. along the medial margin of the frontal lobe, while the other parts situated ventromedially in the thalamus project to the lateral portions of these strips, i.e. along the lateral margin of the frontal lobe. These data provide an alternative view of the organization of the thalamus and suggest that this structure contains a matrix of longitudinal cell columns which in some cases extend across specific nuclear borders and may represent the basic thalamic building blocks in respect to the thalamo-cortical connexions.

Animals↗

Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: II. Hue.

Rhesus monkeys were trained to discriminate successively presented hues. The smallest difference they could reliably detect was determined before and after either inferotemporal ablation, or a lesion intended to remove as much as possible of prestriate area V4 (Zeki, 1973). As a group, the animals with lesions of V4 showed good but not perfect retention of their preoperative performance, and their thresholds were unaltered. The inferotemporal group showed no retention of the simplest successive task, red versus green, but after relearning their thresholds too were unaltered. It appears that animals without inferotemporal cortex can form precise internal representations of hues, and that the basis of the inferotemporal learning impairment may depend upon the nature of the stimuli to be discriminated.

Animals↗

Visual cortex ablation and thresholds for successively presented stimuli in rhesus monkeys: I. Orientation.

Rhesus monkeys were trained to discriminate gratings of different orientation presented one at a time. The smallest difference they could reliably detect was determined before and after removal of either inferotemporal, foveal prestriate or lateral striate cortex. Four animals with inferotemporal lesions had significantly higher thresholds after operation, which did not improve after extensive practice. Two monkeys with lateral striate ablation, and 1 out of 3 animals with foveal prestriate lesions were also impaired, but improved with practice. Monkeys without inferotemporal cortex may have imprecise internal templates for stimulus orientation, in accordance with the categorisation hypothesis of the inferotemporal defect.

Animals↗

Projections from inferior temporal cortex to prefrontal cortex via the uncinate fascicle in rhesus monkeys.

In five rhesus monkeys (Macaca mulatta) we used anterograde and retrograde tracing techniques to investigate the projection from the inferior temporal cortex (area TE) to the prefrontal cortex as well as the course of the projecting fibers. The results showed that TE projects to both the inferior convexity and orbital surface of prefrontal cortex and that these projections course almost exclusively via the uncinate fascicle. Transection of the uncinate fascicle deprives the prefrontal cortex of virtually all input from TE, but leaves intact inputs from prestriate and parietal visual areas as well as the amygdala. Such transection also leaves intact many projections from TE to targets other than the prefrontal cortex, including the amygdala, ventral putamen, tail of the caudate nucleus, and pulvinar.

Amino Acids↗

Nicardipine releases sustained coronary arterial constriction induced by acetylcholine in the rhesus monkey.

In five rhesus monkeys (Macaca mulatta) the vascular bed of the left anterior descending coronary artery (LAD) was perfused at constant pressure with autologous blood. Nicardipine (1-30 micrograms), a dihydropyridine calcium antagonist when injected into the LAD, increased LAD flow without producing significant changes in other cardiohemodynamic variables. With continuous infusions of acetylcholine into the LAD, the flow decreased by about 34% of the basal value. Under these conditions, intra-LAD nicardipine produced an increase in LAD flow almost to the same extent as in the control. The effects of nicardipine were qualitatively similar to those of other calcium antagonists observed in previous experiments and indicate that nicardipine would be useful as an antianginal drug.

Acetylcholine↗

Regulation of hypothalamic luteinizing hormone-releasing hormone levels by testosterone and estradiol in male rhesus monkeys.

Castration of rhesus monkeys produces hypersecretion of pituitary luteinizing hormone (LH) and a marked reduction in hypothalamic luteinizing hormone-releasing hormone (LH-RH) content. We performed the present study to determine whether treatment with gonadal steroids would reverse the effect of castration by increasing LH-RH content. We found that, when administered in doses that suppressed serum LH, both testosterone (T) and estradiol (E) significantly increased LH-RH in the infundibular nucleus/median eminence. The LH-RH content of 8 other regions, some known to contain LH-RH neurons, was not significantly affected. Thus, gonadal steroids act within a discrete region of the basal hypothalamus to modify LH-RH content. The finding that both T and E were effective in male monkeys supports the hypothesis that aromatization is involved in the negative feedback mechanism.

Animals↗

The effects of chronic administration of LH-RH agonists and antagonists on the menstrual cycle and endometrium of the rhesus monkey.

Regularly cycling rhesus monkeys (Macaca mulatta) were used to study the effects of prolonged administration of LH-RH analogs on the menstrual cycle and the endometrium. According to the treatment, animals were divided into: Group 1, vehicle; Group 2, LH-RH agonist (D-Trp6 LH-RH, 20 micrograms/day); and Group 3, LH-RH antagonist [( N-Ac-D-Trp1,3, D-p-Cl-Phe2,D-Arg6,D- Ala10 ]-LH-RH,200 micrograms/day) for 90 days. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P) were measured every second day until thirty days past the discontinuation of drug administration. Endometrial biopsies were obtained on days 10, 40, 90 and 120 and processed for histologic exam and determination of estrogen (E) and progesterone receptors. Animals of Group 1 presented regular cycles, while those in Groups 2 and 3 remained anovulatory throughout the treatment. Animals of Group 2 presented different degrees of endometrial hyperplasia during treatment and animals of Group 3 showed either resting or atrophic endometrium. Administration of LH-RH agonist produced a marked increase in E and P endometrial receptors and the antagonist produced a decrease in P receptors. In both instances, reversal of the effects on the menstrual cycle and in the endometrium was observed 30 days after discontinuation of drug administration.

Animals↗

Dermal penetration of avermectin B1a in the rhesus monkey.

Forearms of rhesus monkeys were treated with [3H]avermectin B1a in three different vehicles and concentrations so that the penetration of avermectin B1a through skin could be determined. In order to simulate exposure of farm workers, such as mixer-loaders, applicators, and harvesters, to this pesticide, avermectin B1a was applied to the forearms of the monkeys as an emulsifiable concentrate (300 micrograms/monkey), a diluted emulsifiable concentrate (4.5 micrograms/monkey), and as a suspension in water (216 micrograms/monkey). After 1 or 10 hr of exposure, the treatment area was washed. The levels of radioactivity were determined in the urine, feces, plasma, and wash. On the basis of the amounts of radioactivity excreted in the urine and feces and the levels of radioactivity in the plasma after dermal application compared to those found after intravenous administration of the compound, less than 1% of the doses was absorbed. These data indicate that avermectin B1a would not readily penetrate the skin of farm workers exposed to it. Therefore, the hazard to farm workers exposed to this compound would be substantially mitigated.

Animals↗

Effects of anticholinergic drugs on DRL performance of rhesus monkeys.

Four adult rhesus monkeys were trained to stable performance baselines on a differential reinforcement of low rates (DRL) 28 sec schedule for food pellet presentation. The effects of graded doses of atropine SO4, benactyzine HCl, and scopolamine HBr on performance were studied. All three anticholinergic compounds produced dose-related decreases in the number of food pellets earned. The number of responses was decreased only by the highest scopolamine dose. The unimodal peak of interresponse times (IRTs) was flattened under drug conditions such that there were roughly equal frequencies of responding in all IRT intervals. Drug potencies for producing these effects were: scopolamine greater than atropine greater than benactyzine.

Animals↗

Effects of cholinergic drugs on delayed match-to-sample performance of rhesus monkeys.

Three adult rhesus monkeys were trained to stable performance baselines on a delayed match-to-sample (DMS) procedure. Subject-initiated trials resulted in brief presentations of a sample color stimulus (red, green, or blue) with matching performance tested after retention intervals of 0, 4, 8, and 16 seconds. The effects of graded doses of atropine SO4, benactyzine HCl and physostigmine salicylate on performance were studied. Only atropine produced a clear interaction between drug and retention interval with the greatest impairments being observed at the longest delays. Benactyzine only affected overall error rates, while physostigmine did not disrupt matching accuracy. The two highest doses of each compound produced reliable elevations in session times and drug-specific changes in the pattern of performance. The results with atropine confirm and extend previously reported work with scopolamine indicating a critical role for cholinergic mechanisms in short-term memory.

Acetylcholine↗

Naloxone reversal of stress-induced reproductive effects in the male rhesus monkey.

Adolescent male rhesus monkeys, stressed by placement in tethering systems, were administered naloxone to discern the involvement of endogenous opioids in the stress-induced reproductive dysfunction. Stressed monkeys exhibited decreased plasma levels of luteinizing hormone (LH), testosterone, and increased levels of prolactin. Administration of naloxone temporarily returned hormone levels to non-stressed values. Stress depressed sexual activity was increased following naloxone treatment. GnRH administration stimulated plasma LH and testosterone levels. These results indicate that stress-induced changes in reproductive function may be mediated by opioids at levels above the pituitary.

Animals↗

Effect of dietary chronic cadmium exposure on cell-mediated immune response in rhesus monkey (Macaca mulatta).

Rhesus monkeys (Macaca mulatta) were daily exposed orally to cadmium (Cd) at 5 mg/kg body wt in diet for a period of 2 and 6 months. Significant amount of Cd accumulated in liver, kidney and spleen after its exposure to monkeys. Cell mediated immune response was assessed by the responsiveness of peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). Even after 6 months of exposure, Cd increased DNA synthesis, although not significantly, in unstimulated and mitogen stimulated lymphocytes. Stimulation Index (SI), however, decreased largely due to increased unstimulated [( 3H]thymidine incorporation) observed after Cd exposure. It, therefore, indicates that Cd is not immunosuppressive in primates, phylogenetically closer to humans.

Animals↗

Afferent subcortical connections into the motor cortical larynx area in the rhesus monkey.

In three rhesus monkeys (Macaca mulatta), the inferior motor cortex was explored by electrical stimulation for sites yielding vocal fold adduction. The retrograde tracer wheat germ-agglutinin-conjugated horseradish peroxidase was injected into the effective sites. Within the forebrain, retrogradely labeled cells were found in the claustrum, basal nucleus of Meynert, substantia innominata, extended amygdala, lateral and posterior hypothalamic area, field H of Forel, and a number of thalamic nuclei with the strongest labeling in the nuclei ventralis lateralis, ventralis posteromedialis, including its parvocellular part, medialis dorsalis and centrum medianum, and weaker labeling in the nuclei ventralis anterior, ventralis posterolateralis, intermediodorsalis, paracentralis, parafascicularis and pulvinaris anterior. In the midbrain, labeling was found in the deep mesencephalic nucleus, ventral tegmental area, and substantia nigra. In the lower brainstem, labeled cells were found in the pontine reticular formation, median and dorsal raphe nuclei, medial parabrachial nucleus, and locus coeruleus. The findings are discussed in terms of the possible role of these structures in voluntary vocal control.

Afferent Pathways↗

Interactions between Mycobacterium leprae and simian immunodeficiency virus (SIV) in rhesus monkeys.

Groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (SIV)B670 alone; 2) Mycobacterium leprae alone; 3) SIV plus M. leprae on the same day; and 4) M. leprae 2 weeks after SIV. Animals were monitored at intervals for virus loads, antibody responses to M. leprae glycolipid antigens and to SIV Gp120, T-cell CD4+ and CD4+ CD29+ subset percentages, leprosy and acquired immunodeficiency syndrome (AIDS) clinical symptoms. Five out of six animals developed leprosy in each co-inoculated group, compared to one out of six in the M. leprae-only-inoculated group, indicating that M. leprae/SIV co-infection increases the susceptibility to leprosy, regardless of the timing of the two infections. Animals in the co-infected group that received M. leprae 2 weeks after SIV had a significantly slower rate of AIDS progression and long-term survival was significantly greater (three out of six) compared to the group inoculated with SIV alone (zero out of seven). All M. leprae-only-inoculated animals (six out of six) survived. Post-SIV-inoculation, a rapid decrease in the percentages of CD4 + and CD4 + CD29 + T-cells was observed in the SIV-only-inoculated group that was significantly blocked by co-inoculation with M. leprae 2 weeks after SIV, but not by SIV on the same day. The virus load set point was increased by approximately two logs in the group inoculated with M. leprae and SIV on the same day compared to SIV 2 weeks prior to M. leprae or the SIV-only-inoculated group. The results indicate that M. leprae, inoculated 2 weeks after SIV, decreased the pathogenicity of SIV compared to inoculation of M. leprae and SIV on the same day or SIV alone. The decreased pathogenicity correlated with a diminished loss of CD4 + and CD4 + CD29 + T-cell subsets in the group inoculated with M. leprae 2 weeks after SIV compared to the group inoculated with SIV alone. IgG antibody responses to M. leprae-specific cell wall phenolic glycolipid-I antigen were inhibited by 2-week-prior or same-day SIV co-inoculation compared to M. leprae-only inoculated animals. The IgG anti-lipoarabinomannan antibody response was enhanced in the group inoculated with M. leprae and SIV on the same day compared to the groups inoculated with M. leprae alone or SIV 2 weeks prior to M. leprae. Antibody responses to SIV Gp120 antigen were unimpaired in both co-inoculated groups compared to SIV-only-inoculated groups. The antibody results show that the immune responses to SIV and M. leprae are interrelated in SIV/M. leprae co-infected animals.

Animals↗

Long-term effects of neonatal damage to the hippocampal formation and amygdaloid complex on object discrimination and object recognition in rhesus monkeys (Macaca mulatta).

Rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex were tested on concurrent discrimination learning (24-hr intertrial interval [ITI]) at 3 months, on object recognition memory (delayed nonmatching-to-sample [DNMS]) at 10 months, and retested on both tasks at 6-7 years of age. Neonatal amygdaloid damage mildly impaired acquisition at the 24-hr ITI and the performance test of DNMS at both ages. In contrast, early hippocampal lesions impaired performance only on the longest lists of 10 items in DNMS in adult monkeys. Thus, early amygdala lesions appeared to have resulted in a greater object memory loss than early hippocampal lesions. However, in light of recent findings from lesion studies in adult monkeys, the object memory impairment after early amygdaloid lesions is better accounted for by damage to the entorhinal and perirhinal cortex than by damage to the amygdaloid nuclei.

Amygdala↗

Menstrual cycle influences on operant behavior of female rhesus monkeys.

Nine female rhesus monkeys were paired with males throughout 63 menstrual cycles. The females' motivation to approach males was studied with an operant conditioning paradigm that required the female to press a lever 250 times to gain access to the male. Sexual behavior was scored during standard 60-min tests that followed the attainment of access (17 pairs, 1,440 tests). In the overall data, mean times to access were shortest at mid-cycle and longest just before and after the onset of menstruation, and a model-fitting method showed that 45% of cycles from individual pairs were significantly correlated with a V-shaped model of the overall pattern. Male sexual activity was highest at mid-cycle and lowest in the last quarter of the cycle, but the changes in access times could not be attributed entirely to the rewarding effects of the ejaculations. In the combined data from five females (9 pairs, 33 cycles), high estradiol levels and low progesterone levels were statistically associated with short access times and short ejaculation times. The overall effect was for operant performance and sexual activity to be synchronized and maximized in the periovulatory period of the menstrual cycle.

Animals↗