Abnormal social development of protein-malnourished rhesus monkeys.

Reports results of an experiment with 2 groups of 5 rhesus monkeys. Ss fed diets deficient in protein (3.5% casein) exhibited social behaviors qualitatively different from controls fed diets sufficient in protein (25% casein). In general, the protein-malnourished Ss showed a lack of reciprocal responsiveness to social initiations, aggression, and a predominance of nonsocially-directed behaviors when compared to controls. Results are discussed in terms of a nutritional-environmental interaction that produces abnormal and possibly long-term deficits in social development. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frustration and self-aggression in social isolate rhesus monkeys.

Compared the frequency of self-aggressive behavior emitted by 6 partial social isolate and 6 socialized rhesus monkeys under baseline living conditions and a continuous reinforcement-extinction schedule of leverpressing. Under baseline conditions, male isolates showed higher levels of self-aggressive behavior than did the female isolates. Further, frustration produced by extinction of the leverpressing response produced a significant but transitory intensification of self-aggressive behavior. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peers as primary attachment sources in yearling rhesus monkeys (Macaca mulatta).

Peer bonds were examined in 2 experiments using juvenile rhesus monkeys to determine (1) whether specific attachment bonds are formed between age-mates, (2) whether preferred age-mates can provide a secure base, and (3) whether a previous attachment bond affects the quality of subsequent attachment bonds. In Exp 1, 8 peer-only reared (POR) monkeys demonstrated a specific preference for a predicted favorite peer when given a choice between a familiar and 2 unfamiliar peers. In Exp 2, POR Ss were placed in a novel setting with either their most preferred peer, a familiar but not preferred peer, or an unfamiliar peer, and their responses were compared with those of a 2nd group of monkeys, reared for their 1st 6 mo of life by their mother. Both mother-reared (MP) and POR monkeys displayed significantly more intimate contact and significantly less distress when with their most preferred peer; nevertheless, even when they were with their most preferred peer, POR Ss exhibited more distress than MP Ss. Findings are discussed with reference to current attachment theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ejaculation on levels of testosterone, cortisol, and luteinizing hormone in peripheral plasma of rhesus monkeys.

In 3 experiments, the 1st 2 of which were conducted 1 yr apart, plasma levels of testosterone (T), luteinizing hormone (LH), and cortisol were measured in 10 adult male rhesus monkeys before and shortly after coitus. Mean levels of T and LH did not increase significantly after coitus or in control (no ejaculation) tests, but cortisol levels did in both cases. In 10 different males, no significant change was found in the plasma levels of T after electroejaculation; but in control tests (electric current withheld), the mean level of T was significantly lower at 80 and 140 min, but not at 50 min, after the test. According to present evidence, the effect of ejaculation on T levels differs in primate and nonprimate species. The effects on T levels produced by living with sexually receptive female rhesus monkeys may differ from those produced by intimate but brief contact with them. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of differential pretraining on learning-set formation in rhesus monkeys.

Compared the rate of learning-set formation by 4 rhesus monkeys that had previously been pretrained on the win-stay component of the learning-set strategy (Group WS) to the rate evidenced by 4 others that had pretraining on the lose-shift component (Group LS). Differences between groups were small, and asymptotic levels were below those previously obtained by monkeys without pretraining. The negative transfer resulted from generalized tendencies to perseverate or shift (Groups WS and LS, respectively), regardless of response outcome. The former tendency dissipated relatively rapidly, while the latter persisted very markedly throughout the 400-problem learning-set series. It is noted that learning-set formation requires a balance between the win-stay and lose-shift components; however, the optimal ratio is unknown. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical examination of visual and social responses in infant rhesus monkeys.

Obtained normative data from a battery of tests (e.g., pupillary response, sound localization, orienting, and face reaction) administered to evaluate simple visual functions in 15 infant rhesus monkeys. Visual responsiveness was limited to simple reflexes in the 1st days of life, but it developed rapidly. By the 2nd wk, Ss reached for objects and responded socially to faces with both gaze aversion and lipsmacking. However, social responsiveness developed differently in males and females: Males responded to faces with lipsmacking 4 days after responding with gaze aversion, while females showed both responses for the 1st time on the same day. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social and nonsocial behaviors of adult rhesus monkeys after amygdalectomy in infancy or adulthood.

At 6 yrs of age, 6 female rhesus monkeys that had sustained bilateral amygdalectomy in infancy and 5 intact controls were transferred to an observation cage where behaviors were recorded while the Ss were alone, paired with unfamiliar stimulus animals, and paired with familiar Ss from the opposite experimental group. The 5 adult controls then underwent amygdalectomy, and all tests were repeated with the infant- and adult-operated Ss. Infant-operated Ss changed behaviors more rapidly than did intact controls in social and nonsocial situations, and their activity levels were less modified after a 24-hr period in the observation cage. They were subordinate to intact controls but expressed less fear than did controls when briefly placed with an unfamiliar aggressive animal. Adult amygdalectomy produced many changes in behavior, but these were identical to those observed in like-age monkeys that had been amygdalectomized in infancy. Infant-operated monkeys demonstrated more behavioral deficits at 6 yrs than they had earlier in life. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Face scanning and responsiveness to social cues in infant rhesus monkeys.

Investigated the development of gaze aversion in 8 infant rhesus monkeys (Macaca mulatta) by recording their visual fixations while they scanned pictures of monkey faces looking back at them and pictures of monkey faces looking away. During the 1st week of life, Ss inspected the 2 face-types equally. During Weeks 3 and 7, however, they inspected the faces looking back less than the faces looking away. The maturation of selective viewing was not paralleled by changes in scanning strategies (e.g., by a shift from scanning the contours of faces to fixations of internal details). The implications of early species-typical social awareness for social and perceptual development in rhesus monkeys are discussed. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of clonidine, dexmedetomidine and xylazine on thermal antinociception in rhesus monkeys

The antinociceptive effects of the s.c. administration of the alpha-2 agonists clonidine (0.0032-1.0 mg/kg), dexmedetomidine (0.001-0.032 mg/kg) and xylazine (0.1-3.2 mg/kg) were examined in the warm-water tail withdrawal assay in rhesus monkeys. The three agonists were dose-dependently effective in this assay; their potency order being dexmedetomidine > clonidine > xylazine. The alpha-2 antagonist idazoxan (0.1-3.2 mg/kg) caused dose-dependent and roughly parallel rightward shifts in the dose-effect curves for the three agonists. Apparent pA2 analysis with idazoxan yielded homogeneous values for the three agonists, supporting the notion that similar receptors mediate their antinociceptive effects. The opioid antagonist quadazocine (1.0 mg/kg) did not antagonize the antinociceptive effects of clonidine and xylazine, indicating that opioid receptors do not participate in the effects of the compounds in this assay. At dose ranges found to be effective in the antinociceptive assay, clonidine, dexmedetomidine and xylazine also dose-dependently caused sedation, muscle relaxation, bradycardia and moderate respiratory depression. The sedative, muscle relaxant and respiratory depressant effects of xylazine could be antagonized by idazoxan, suggesting that these effects may be mediated through alpha-2 receptors. These data indicate that the three imidazoline alpha-2 agonists, clonidine, dexmedetomidine and xylazine are effective s.c. in the warm-water tail withdrawal assay in rhesus monkeys, but only at doses that produce other behavioral and physiological effects.     

Effects of chronic caffeine administration on respiration and schedule-controlled behavior in rhesus monkeys

The effects of chronic caffeine administration on ventilation and schedule-controlled behavior were studied in 12 adult rhesus monkeys. In seated subjects prepared with a head plethysmograph, ventilation was measured during exposure to air (normocapnia) and to elevated levels of CO2 (3%, 4% and 5%) mixed in air (hypercapnia). Acute administration of caffeine (10.0-30.0 mg/kg i.m.) produced marked, dose-dependent increases in ventilation during conditions of normocapnia and hypercapnia. However, daily administration of caffeine (10.0 mg/kg i.m.) for 8 consecutive days resulted in tolerance to its respiratory-stimulant effects that was surmountable with higher doses. Caffeine-tolerant subjects also were cross-tolerant to theophylline, an active metabolite of caffeine, and to rolipram and Ro 20-1724, selective phosphodiesterase inhibitors. When chronic administration was terminated and the acute effects of caffeine were redetermined, sensitivity returned to levels obtained before chronic administration within 9 days. Drug effects on behavior were studied in monkeys trained to respond under a fixed-interval schedule of stimulus termination. Acute administration of caffeine (1.0-30.0 mg/kg i.m.) produced significant rate-increasing effects on fixed-interval responding, but chronic administration resulted in tolerance that was insurmountable, such that no dose increased responding above control rates. Although the time course for development and loss of tolerance to the behavioral effects of caffeine corresponded closely with respiration, cross-tolerance did not extend to the behavioral effects of rolipram. Chronic caffeine administration had little effect on caffeine metabolism or clearance, which indicated that caffeine tolerance was pharmacodynamic. The results suggest that different neurochemical mechanisms mediate the effects of caffeine on respiration and behavior, and that inhibition of type IV phosphodiesterase plays a prominent role in caffeine-induced respiratory stimulation.     

Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood

Monocyte chemotactic peptide-1 (MCP-1) belongs to a large family of cytokines known as chemokines. It is a potent mediator of inflammatory response and is thought to play a major role in recruiting monocytes into the site of inflammation. Mixed cryoglobulinemia is a systemic vasculitis characterized in 10 to 30% of the cases by renal involvement. Monocyte infiltration into the glomerulus, and in the periglomerular and perivascular areas is a common histopathological feature of this form of glomerulonephritis. We sought to determine, by in situ hybridization and immunohistochemistry, the renal gene and protein expression of MCP-1 in cryoglobulinemic glomerulonephritis compared to normal kidney, and to correlate it with macrophage infiltration. Kidney biopsy specimens were obtained from 9 patients with cryoglobulinemic glomerulonephritis and 9 control kidneys. The distribution and intensity of MCP-1 gene and protein expression, and the macrophage infiltration (CD68 positive cells) were evaluated and quantitated by a computerized image analysis system. In normal kidneys, MCP-1 was weakly expressed, both at the gene as well as at the protein level. In diseased kidneys, a statistically significant (P < 0.001) up-regulation of MCP-1 gene and protein expression was found, particularly within the areas of tubulointerstitial damage and the glomeruli. By means of CD68 positive cells, a significant correlation (P < 0.001) was found between glomerular, tubulointerstitial macrophage infiltration and MCP-1 expression. Moreover, by combining immunohistochemistry and in situ hybridization, we observed the presence of CD68 positive cells mainly, if not exclusively, around the cells expressing MCP-1 mRNA. Interestingly, a striking increase in MCP-1 urinary concentration was found in cryoglobulinemic patients. In conclusion, our data suggest that MCP-1 may play a major role in modulating the inflammatory process observed in cryoglobulinemic glomerulonephritis.     

Effects of 17 alpha-dihydroequilenin sulfate on atherosclerotic male and female rhesus monkeys

OBJECTIVES: Our purpose was to determine the effects of 17 alpha-dihydroequilenin on plasma lipid and lipoprotein, glucose, and insulin concentrations; coronary artery vasomotor function; and reproductive organ and mammary gland proliferation in atherosclerotic male and female rhesus macaques. STUDY DESIGN: Fifty adult female and 33 adult male rhesus macaques were randomized to treatment by lifetime dietary cholesterol exposure and ratio of total plasma cholesterol to high-density lipoprotein cholesterol. The female treatment groups were intact female controls (n = 9), ovariectomized controls (n = 16), ovariectomized plus 0.3 mg/kg/day 17 alpha-dihydroequilenin (n = 17) and ovariectomized plus subcutaneous estradiol (n = 7). The male treatment groups were control (n = 16) and 1.25 mg/kg/day 17 alpha-dihydroequilenin (n = 17). Treatment lasted 5 weeks. Longitudinal assessments of plasma lipid and lipoprotein and glucose and insulin concentrations were performed. Coronary artery vasomotor function was assessed by quantitative coronary angiography 1 week after initiation of treatment. Morphologic and immunohistochemical assessments of proliferation index values of reproductive organs and mammary glands were done at necropsy. RESULTS: 17 alpha-Dihydroequilenin prevented endothelium-dependent vasoconstriction in males (p < 0.05) and ovariectomized females (p < 0.08). 17 alpha-Dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p < 0.05) and lowered fasting insulin concentrations (p < 0.05) without changing fasting plasma glucose concentrations in males. 17 alpha-Dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. It had no trophic effects on uterus, endometrium, or breast. There was no effect on either prostatic or testicular weight. CONCLUSION: 17 alpha-Dihydroequilenin may represent a single-agent hormone therapy for reduction of ischemic hear disease risk for both menopausal women and men. It has no apparent trophic effects on reproductive organs or mammary glands of female and male rhesus macaques.     

Short- and long-term effects of repetitive mother–infant separations on social development in rhesus monkeys.

Rhesus monkey mother–infant dyads were each subjected to 16 4-day physical separations between the infants' 3rd and 9th mo of life. Infants displayed protest behavior following each separation but only minimal signs of despair. Their protest diminished somewhat over repeated separations. The mothers' separation reactions were considerably milder (and changed little) over repeated separations. The separations appeared to retard the development of normal mother–infant relationsips: Relative to nonseparated control dyads, separated infants displayed excessive levels of infantile behaviors, although their mothers did not differ from control mothers in levels of any behavior. Near the end of their 1st yr, all infants were permanently separated from their mothers and housed as peer groups. Over the next 30 wks during peer housing, few behavioral differences emerged between previously separated and control Ss. However, when exposed to their mothers during preference tests, previously separated Ss seemed to avoid their mothers in sharp contrast to the mother-seeking activity displayed by control infants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Follow-up study of isolation-reared and mother-reared rhesus monkeys paired with preadolescent conspecifics in late infancy: Cross-sex pairings.

8 rhesus monkeys, 4 of each sex, which had been reared either with their mothers or in social isolation during early infancy, were paired with preadolescent conspecifics during late infancy. Some isolate-reared Ss appeared to have gained from this social experience. At nearly 3 yrs of age, each S was paired (sequentially) with 2 other-sex animals (1 isolate- and 1 mother-reared) after having been housed alone for the entire 2nd (and most of the 3rd) yr of life. Little social interaction occurred between the members of any pair. Several significant effects of rearing experience indicated that social experience with preadolescents in late infancy did not permanently reverse the deleterious effects of early isolation. However, the mother-reared Ss also failed to establish social rapport with one another. Comparison of these results with those of similar research employing mother-reared animals which had received supplemental social experience during the 2nd yr of life suggests that such social experience is of some importance for optimal development of later sociosexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of early social deprivation on emotionality in rats.

Following parturition, 95 male Holtzman albino rat pups were separated from their mothers and randomly assigned to rearing conditions (a) with mother and peers, (b) with mother without peers, (c) in incubators with peers, or (d) in incubators in isolation. At 65 days of age Ss were tested daily in an open field for 3 min. over 6 consecutive days. At 113 days of age, Ss were restrained and presented a mild auditory stimulus and subsequently a noxious shock stimulus while heart rate recordings were taken. Higher emotionality in maternally-deprived Ss was evidenced in longer emergence latencies, lower ambulatory scores, and higher urination frequencies in the open field. Maternally-deprived Ss also gave larger heart rate responses to auditory and shock stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early experience and complexity of social organization in groups of young rhesus monkeys (Macaca mulatta).

Found that 2 6-member social groups of young rhesus monkeys, one socially deprived and the other raised with mother and age-mates, showed marked differences in the complexity of social organization. Compared to deprived Ss, experienced Ss interacted more often as trios and larger subgroups, and the response structure of their triadic subgroups was more complex. Only in the experienced group did functional aspects of triadic interactions suggest that 1 individual recognized the status relations between the other participants. These findings indicate that early social experience affects levels of social competence that transcend variations in ethologically derived response patterns and that cannot be seen in arranged dyadic encounters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of some phenylethylamines in rhesus monkeys trained to discriminate (+)-amphetamine from saline

The distribution of intraepithelial nerve fibres and neuroendocrine cells within the surface and glandular epithelium of human nasal mucosa and larynx was examined using immunohistochemical techniques. Neuronal structures were immunostained for the general neuroendocrine marker protein gene-product (PGP) 9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings contained PGP 9.5 and were found within the respiratory surface epithelium of the nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these nerve fibres showed positive immunoreactivties with antibodies against SP and CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts passing the basal membrane and reaching the luminal part were detected. These nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of nerve fibres within the squamous surface epithelium was detected in the subglottic and epiglottic region containing CGRP and SP in a small subpopulation of nerve fibres. Single intraepithelial taste buds in the epiglottic region and neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.     

The development of stereoacuity in infant rhesus monkeys

The emergence of stereopsis at 3-4 months postnatal in human infants is striking and has led to speculation that its rapid onset and subsequent development must be due to a dramatic reorganization of the brain. Stereopsis has never been measured in infant monkeys, but previous studies have demonstrated that many other visual functions develop four times faster in infant monkeys than in humans. We made longitudinal assessments of stereoacuity in 11 infant rhesus monkeys. A forced-choice preferential-looking technique was used to present random-dot stereograms during testing. By 8 weeks after birth, all of the monkeys were responding to at least coarse levels of disparity (1760" [seconds]), and by 13 weeks of age, all were responding to the relatively fine level of 88" disparity. Age of onset for stereopsis in monkeys was at about one-quarter the age when it occurs in humans, as expected. However, subsequent development proceeded at a similar absolute rate in monkeys and humans. The findings are discussed relative to the neural mechanisms which might be responsible for the differing rates of development.     

Drug dependence study on vigabatrin in rhesus monkeys and rats

The dependence potential of vigabatrin (gamma-vinyl GABA; R(-)/S(+)-4-amino-5-hexenoic acid, CAS 60643-86-9, MDL 71,754) was assessed in rhesus monkeys and rats. In the test of cross physical dependence potential, morphine- and barbital-dependent monkeys were both withdrawn from the respective drugs and the ability of vigabatrin to suppress the withdrawal signs was assessed. In morphine-dependent monkeys, subcutaneous doses of vigabatrin at 256 and 1000 mg/kg did not suppress withdrawal signs while subcutaneous doses of codeine phosphate at 4 and 8 mg/kg clearly suppressed the withdrawal signs. In barbital-dependent monkeys, subcutaneous and intravenous dose of vigabatrin, both at 1000 mg/kg, did not suppress the withdrawal signs, while intragastric doses of diazepam at 8 and 16 mg/kg clearly suppressed them. Thus, while the cross-physical dependence potential of codeine/morphine and of diazepam/barbital was clearly observable, vigabatrin appeared to have no such potential. In the test of physical dependence-producing potential with the drug-admixed food method in rats, vigabatrin and diazepam were given to rats mixed with food for 28 days in an increasing dosage schedule, followed by feeding a drug-free diet to observe withdrawal signs for 7 days. Upon withdrawal, no decrease in food intake or body weight was observed in the vigabatrin-treated groups, and the gross condition of the animals did not differ from that in the control group. In contrast, food intake and body weight decreased markedly in the diazepam group, and most rats showed hyperreactivity to external stimuli. Thus, while the physical dependence-producing potential of diazepam was clearly demonstrated, such potential was not shown with vigabatrin. In the test of reinforcing effect, 4 monkeys were allowed to self-administer pentobarbital at 1 mg/kg/infusion, or vigabatrin at 16, 32, and 64 mg/kg/infusion, intravenously through an indwelling catheter. Each drug was preceded and followed by saline self-administration for at least 7 days. Active self-administration of pentobarbital was observed in all monkeys tested, while the self-administration rate of vigabatrin did not differ from saline. Thus, while the reinforcing effect of pentobarbital was clearly observed, such effect was not observable with vigabatrin. Based on these results, it was considered that vigabatrin was devoid of dependence potential.     

Respondent conditioning of self-injurious behavior in early socially deprived rhesus monkeys (Macaca mulatta).

Examined whether certain environmental events could elicit self-injurious behavior (SIB) and whether the resulting SIB could be conditioned to an antecedently presented external stimulus. Exp I showed that SIB could be elicited in 4 socially isolated rhesus monkeys by the application of brief, mild, electric footshock. In Exp II, 3 socially isolated Ss were exposed to a procedure that paired a 10-sec tone with a 1-sec electric footshock. Three control Ss received presentations of the tone alone. Results show that Ss in the experimental group began to show SIB during the tone periods, thereby providing evidence of respondent conditioning. Data expand the scope of the learning model of SIB from primarily operant interpretations to respondent conditioning as well. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)