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Tissue sites of aromatization in the female rhesus monkey.

Nine female rhesus monkeys (four in the follicular and five in the luteal phases of their cycles) had catheters implanted and were infused iv with [7-3H]androstenedione (A) and [4-14C]estrone (E1) for 4 h. Blood samples were drawn at intervals from the hepatic, renal, jugular, uterine, and brachial veins and the femoral artery. The samples were analyzed for radioactivity as A and E1. The mean +/- SE MCRs for A and E1 were 280 +/- 40 and 270 +/- 30 liters/day, respectively. The mean extractions across the liver measured in six of the monkeys were 0.83 +/- 0.03 for A and 0.71 +/- 0.06 for E1. The percentage of A entering each tissue, which was measured as E1 leaving the tissue (pA,E1AV), was 0.20 +/- 0.10 for splanchnic, 0.21 +/- 0.11 for renal, 0.46 +/- 0.21 for jugular, 2.36 +/- 1.27 for arm, and 0.35 +/- 0.10 for uterine veins. Because of the sampling technique, the value for the uterus may be a reflection of ovarian blood admixture with uterine blood. There were no apparent differences in tissue aromatization between values in the follicular and luteal phases of the cycle. The overall mean value for the percentage of A infused and measured as E1 in arterial blood (pA,E1BB) was 1.01 +/- 0.38%. Using previously reported tissue blood flow, we calculate that the contributions to the overall aromatization rate of tissues drained by the brachial, renal, jugular, hepatic, and uterine veins are 23%, 5%, 5%, 4%, and 0.2%, respectively. Thus, the splanchnic tissue is a minor site for extraglandular aromatization of androgens in the rhesus monkey. An important site appears to be the arm, which reflects aromatization in adipose tissue, muscle, skin, and supporting structures.

Androstenedione↗

Drinking in the rhesus monkey: peripheral factors.

Rhesus monkeys prepared with chronic cannulae implanted in the stomach and duodenum were water deprived for 22.5 hr. With both cannulae closed, a mean of 137 ml was drunk within a 60-min period. When ingested water drained freely from an open gastric cannula, continuous drinking far in excess (878 ml mean intake) of normal occurred. Sham drinking also exceeded (634 ml mean intake) normal when ingested water drained through an open duodenal cannula. This pattern of continuous sham drinking indicates that oropharyngeal stimulation is not sufficient alone, or together with the passage of water through the stomach and the initial part of the duodenum, to terminate drinking. Duodenal infusions of water (25-100 ml) slowed or stopped gastric sham drinking in a dose-dependent fashion, but equivalent infusions of isotonic saline were without effect. Thus, pre- or postabsorptive signals at or beyond the level of the intestine distal to the site of the duodenal cannula are probably important for the termination of drinking in the rhesus monkey.

Animals↗

Evolutionary stability of transspecies major histocompatibility complex class II DRB lineages in humans and rhesus monkeys.

Sequence analysis of rhesus monkey (Macaca mulatta) polymorphic second exon of major histocompatibility complex class II DRB subregion genes demonstrates the existence of at least 34 alleles. Some of these rhesus monkey alleles are very similar (or nearly identical) to HLA-DRB alleles. These data demonstrate that members of the lineages for Mhc-DRB1*03, -DRB1*04, -DRB1*10, and the loci of Mhc-DRB3, -DRB4, -DRB5, and -DRB6 predate speciation of man and rhesus monkey and were already present 25 million years ago. Calculation of evolutionary rates suggests that the various allele lineages have differential stabilities. Furthermore, the data indicate that distinct species may not have inherited or lost transspecies Mhc-DRB lineages in evolution, because several allele lineages in rhesus monkeys appear to be absent in humans and vice versa.

Alleles↗

Secondarily generalized convulsive seizures induced by daily amygdaloid stimulation in rhesus monkeys.

Amygdaloid kindling in rhesus monkeys resulted in development of secondarily generalized convulsive seizures in an average of 196 days. Prior pharmacologic (bemegride) kindling accelerated this seizure development in one animal. None of the animals reached the stage 5 primary generalized seizure of baboons (Papio papio), even after 400 daily amygdaloid stimulations. Seizure stage instability, with frequent regression to an earlier stage, and the difficulty of establishing a generalized seizure triggering threshold in most of the rhesus monkeys, contrasts with our experiences in Papio papio. Thus, differences in the speed of kindling and in the quality of kindled convulsion between rhesus monkeys and epileptic baboons probably reflect the presence or absence of an epileptogenic predisposition in these two species. The difficulty of developing convulsive seizure in rhesus monkeys suggests that this species is particularly suited for the study of partial complex seizure. These studies indicate that the abrupt onset of human epilepsy with a fully developed convulsive seizure must represent and overwhelming central pathophysiologic event resulting from an endogenous, exogenous or a combined insult interacting with a genetically predisposed seizure susceptibility.

Amygdala↗

Expression and localization of CFTR in the rhesus monkey surface airway epithelium.

The Rhesus monkey has been used as a model for evaluating the possibility of introducing the CFTR gene into the airway epithelium in vivo. We addressed the question of whether the simian airway surface epithelium exhibits a CFTR distribution and functional activity (ciliary beating frequency) similar to that of human airway surface epithelium. Expression of CFTR mRNA was demonstrated on Rhesus monkey tracheobronchial tissue by reverse transcription polymerase chain reaction (RT-PCR) analysis. By immunofluorescent light microscopy, CFTR was localized on the apical plasma membrane of ciliated cells as we previously described for human tracheobronchial surface epithelium. The ciliary beat frequency (CBF) measured on the explant of Rhesus monkey tracheobronchial tissue appeared to be similar to that of the CBF of human tracheobronchial ciliated cells. To compare the Rhesus monkey CFTR gene with that of the human, we sequenced parts of exon 13 (encoding the R domain) and exon 24 (encoding the C terminal part of the protein) of the Rhesus monkey CFTR gene. The nucleotide sequence identity with the human counterpart was found to be 98% and 94% respectively, although restriction enzyme differences allow discrimination between Rhesus monkey and human CFTR cDNA. Taken together, these results suggest that the airway epithelium of the Rhesus monkey is a suitable model of human respiratory epithelium for analyzing the effect of human CFTR gene transfer.

Amino Acid Sequence↗

Discriminative stimulus effects of naltrexone in morphine-treated rhesus monkeys.

Three adult, female rhesus monkeys responded under a fixed-ratio 5 schedule of stimulus-shock termination while discriminating between s.c. injections of saline and naltrexone (0.01 mg/kg). In addition, monkeys received daily injections of morphine (1.78 or 3.2 mg/kg) 3 hr before experimental sessions. With increasing doses of naltrexone monkeys switched in a dose-related manner from the saline to the naltrexone lever; complete generalization (greater than 80% responding on the naltrexone lever) occurred in all monkeys at doses of naltrexone larger than 0.0032 mg/kg. Doses of naltrexone that produced responding on the drug lever also produced effects typically observed during opioid withdrawal (e.g., miosis and salivation). Compounds with opioid mu antagonist effects under other conditions (e.g., nalorphine) substituted for naltrexone whereas a wide variety of opioid agonists (e.g., morphine, U-50,488 and butorphanol) as well as nonopioids (e.g., pentobarbital and ketamine) produced responding predominantly on the saline lever. Monkeys also switched to the naltrexone lever in a time-related manner after the daily injection of morphine with complete generalization occurring between 8 and 27 hr after morphine. Among a variety of opioid and nonopioid compounds, including drugs used in the treatment of opioid abuse (e.g., clonidine), only compounds with mu agonist actions under other conditions produced a switch in responding from the naltrexone to the saline lever in 27-hr morphine-abstinent monkeys. These results suggest single, daily injections of morphine are sufficient to produce dependence in rhesus monkeys and indicate further drug discrimination studies in morphine-treated rhesus monkeys might be pharmacologically more specific than observational procedures.

Animals↗

The susceptibility of rhesus monkeys to motion sickness.

The susceptibility of rhesus monkeys to motion sickness was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150 degrees/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion tests, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness.

Animals↗

Social separation and reunion affects immune system in juvenile rhesus monkeys.

Removal of juvenile rhesus monkeys from their natal social group to indoor individual caging resulted in increased basal cortisol secretion and significant decrements in the frequency of lymphoid subpopulations. Fourteen juvenile rhesus monkeys, which had never been removed from the group, were studied. Baseline immune and cortisol measurements were obtained before seven of the subjects were removed from social housing to standard individual cages. The remaining seven subjects, matched for age, sex, weight, and rank, remained in the social group throughout the study serving as controls. Blood samples were taken 24 hours after removal of the test subjects from the group and at specific intervals thereafter through 11 weeks. At 24 hours after the separation test subjects showed a significant increase in basal cortisol levels (40%) and a significant decrease in several immune parameters, with absolute numbers of total T cells declining 72 +/- 12%. Significant group differences in immune parameters persisted through 11 weeks. Eighteen weeks following removal, the test subjects were returned to the group which produced a cortisol rise in both test and controls at the 24-hour postreturn sample. Although there were no group differences in the frequency of lymphoid subsets 24 hours after return, some test subjects showed marked decrements which were inversely related to cortisol and were predicted by behavioral events. These data demonstrate that the removal of naive juvenile rhesus monkeys from their natal social group to individual indoor caging is a potent psychosocial stressor and that the behavioral interactions which characterize the return of the individual subjects to the natal group may predict physiological response.

Animals↗