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Three experiments were performed to determine the effect of stress on the neuroendocrine-immune system in nonhuman primates. In Experiment 1 the diurnal variation in cell and hormone levels was determined. The percentages of neutrophils, monocytes, and eosinophils fluctuated throughout the 24-hr period, while white blood cell (WBC), neutrophil-to-lymphocyte ratio (N:L), hemoglobin (Hgb), natural killer cell cytotoxicity (NK activity) and beta-endorphin levels did not. Experiment 2 investigated the effects of ketamine and restraint on behavior. Scratching was increased in control monkeys and animals receiving ketamine, whereas passivity was increased in chair-restrained animals. In Experiment 3, eight adult male rhesus monkeys were restrained in primate chairs at 0600h. Behavior was filmed for 3 hr and blood samples were collected at 0700, 0800, and 0900. Whole blood was analyzed for total WBC and percentage of each leukocyte type. NK activity was also measured. Plasma levels of cortisol and beta-endorphin were determined and behavior was quantitated from video-records. WBC and the percentage of neutrophils increased during the restraint period, while the percent lymphocytes and monocytes decreased. NK activity also decreased over time after restraint whereas plasma cortisol and beta-endorphin levels increased significantly. Although after the 3 hr of restraint stress, changes were found in hormone levels, behavior, and NK activity, there were no significant correlations between the parameters measured. Thus, our results indicate that there is not a common neuroendocrine response or single neuroendocrine mediator that results in predictable behavioral changes and immune suppression following stress.

The development of brain stem auditory evoked responses (BAERs), recorded from a surface electrode as short-latency, volume-conducted potentials, was studied in a series of kittens over a postnatal period ranging from birth to 60 days. Repeated, longitudinal observations on particular kittens were supplemented with observations on additional kittens during the first and second postnatal week to determine age of onset of the BAERs. The position of the animal and sound source within the recording chamber were held constant across recording sessions, as was click intensity except during recordings in which intensity effects were specifically studied. Click rates of 1, 10, 50 and 100/sec were routinely presented. Reference electrodes at the tongue, pinna and neck showed volume-conducted responses to the click stimuli and resulted in considerable distortion of the activity recorded by the vertex electrod; the forepaw, in contrast, showed no activity and a vertex-forepaw electrode configuration provided good resolution of the BAERs across development. A number of new observations were made. BAERs were first observed at 4 days of age, approximately the same age at which depth evoked potentials are first recorded in brain stem auditory nuclei. Initially the BAERs were diffuse, high threshold and fatigued rapidly, characteristics shared with depth evoked potentials in the early postnatal period. Over the first two weeks, the potentials showed marked decrease in threshold, increased resistance to fast click rates, and better definition of wave forms. All BAER components showed exponential decreases in latency. Because all of the brain stem evoked potentials could be recorded concurrently and longitudinally in the same subject a number of developmental comparisons were possible among the BAER components. Wave 1, related to the acoustic nerve in the adult cat, showed a developmental time course and adult latency similar to that reported for N 1 . Wave 2, related to the cochlear nucleus in the adult, showed a marked bimodality over the first month; wave 2a was a large amplitude clearly separated wave which gradually fused as an inconspicuous conspicuous leading shoulder on wave 2b. Wave 2b developed with a time course and adult latency similar to that reported for the ventral cochlear nucleus. Wave 3, related to the region of the superior olivary complex in the adult, showed a clear but transient bimodality during the third week of development. Wave 5, related to the inferior colliculus in the adult, appeared later than waves 1–4 and showed a significantly slower rate of development than waves 1–4. These data indicate that differential developmental changes occur within the brain stem auditory pathway and that the BAERs provide a dynamic probe of concurrent maturational interactions.

Six adult ovariectomized rhesus macaques were given a gonadotropin-releasing hormone (GnRH) antagonist [Ac-β-(2)DNAL 1 ,pFDPhe 2 , DTrp 3 , DArg 6 ]-GnRH, by intravenous infusion for 3 to 3.5 days to determine whether the positive feedback action of estradiol benzoate (E 2 B) on pituitary luteinizing hormone (LH) secretion could be inhibited by blockage of GnRH binding to pituitary gonadotropes. The LH release was suppressed when the antagonist was given either as a bolus injection every 6 hours or as a constant infusion, beginning 24 hours after the E 2 B was administered. Both LH release and follicle-stimulating hormone release were suppressed if the GnRH antagonist infusion began when the E 2 B was administered. The results suggest that continued hypothalamic GnRH stimulation of the pituitary is necessary for the full expression of the preovulatory-like gonadotropin surge that occurs in ovariectomized macaques in response to E 2 .

Five to 20 μg of prostaglandin (PG) E1 infused into the third ventricle of 38 rats on the afternoon of vaginal proestrus reversed the pentobarbital (Pb) blockade of ovulation in 25. Plasma levels of luteinizing hormone (LH) were higher in the PGE1-infused females than in the Pb-blocked controls, but the peak concentrations were only half as high and lasted only half as long as comparable values in normal proestrous females. PGE1 was a more potent stimulator of ovulation in Pb-blocked females than either PGE2 or PGF2α. If infused into the pituitary or injected subcutaneously, however, PGE1 (10 μg) failed to induce ovulation in Pb-blocked animals. The data indicate that PGE1 stimulates LH release and ovulation in the Pb-treated rat by activating a neurally-controlled gonadotropin-releasing mechanism.