Stress primate studies

This suggestion receives support from the observation that chronic stress or glucocorticoid administration has been demonstrated to produce atrophy and death of vulnerable hippocampal neurons in rodents and primates. Furthermore, MRI studies have revealed reduced hippocampal volumes in patients with Cushing s disease... 

Studies on the noradrenergic axis in nonhuman primates provide evidence that early environmental stressors may provoke biological and behavioral phenocopies of human clinical anxiety states. We have used the primate model of developmental psychopathology pioneered by Rosenblum et al. (1991) to explore this issue. Nonhuman primates who were reared as infants by mothers undergoing environmental stress induced by unpredictable or variable foraging demand (VFD-reared) conditions were compared with nonhuman primates reared as infants by mothers exposed to predictable (either low [LFD-reared] or high [HFD-reared]) foraging demand conditions. 

As yet, few attempts have been made to study the effects of pharmacological challenge in individual primates that have been socially stressed or that are temperamentally vulnerable. The success of this approach is illustrated by an important study (Insel et al. 1988) in which peer-reared rhesus monkeys were shown to be especially sensitive to a p-CCE challenge and by our own studies using a behavioral test battery as a screening instrument to identify vulnerable and resistant subjects before administration of CCK-4 (Palmour et al. 1992a). 

As in the human studies, CCK-4 and other peptides must be given to primates intravenously to compensate for the short half-life, but the behavioral stress of short-term administration would confound behavioral observations. The implantation of an indwelling venous catheter that is protected by a jacket and swivel assembly allows administration of peptide or placebo without handling or alerting the animals. Behavioral observations may be made both immediately and from videotape records habituation and daily observations minimize nonspecific behavioral effects. In our own studies, monkeys typically receive placebo, CCK-4, or an analogue intravenously every second or third day but are often videotaped every day. 

Usually both sexes should be used in these studies, excluding non-human primates. The high dose should be above the no observed adverse effect level (NOAEL) but below a level inducing changes secondary to stress. Multiple dose levels are recommended in order to determine dose-response relationships and the dose at which no immunotoxicity is observed. 

Severe neglect during infancy has been studied both in humans and in monkeys. Lasting behavioral consequences seen in lower order primates include impaired affective controls manifested by low frustration tolerance, lability and impulsive behavior, a predominance of aggressive behavior, a tendency to engage in self-mutilation behavior when under stress, and hyperingesting alcohol (characteristics closely resembling symptoms of severe personality disorder). See chapter 11. 

It is difficult to assess the relationship of HEAR oils and other oils high in docosenoic acid content to the development of focal myocardial degenerative lesions in the monkey. In a recent study, a series of 312 hearts were selected at random from monkeys used in unrelated toxicological studies (Qureshi, 1979). The monkeys, which included squirrel (Saimiri sciureus) cynomolgus Macaca fascicularis), rhesus Macaca mulatta) and assam (Ma-caca assamensis) monkeys were of both sexes. Chronic interstitial myocarditis was found in 34% of the monkeys, approximately evenly distributed in males and females (Table IX). The lesions varied from slight necrosis to myocarditis with focal accumulation of lymphocytes, mononuclear cells, plasma cells, and some eosinophiles. Inflammation of the myocardium was distributed throughout the heart. These lesions, which occur frequently in primates, apparently are not related to bacterial, viral, or parasitic infections, but may be related to, and precipitated by, stress (Qureshi, 1979 Soto et al., 1964). 

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