Early experience effects on the development of fear in the squirrel monkey.

This study was conducted to determine whether juvenile squirrel monkeys exposed to a snake for a 60-min episode during the preweaning period display behavioral and physiological responses to a snake similar to those displayed by feral-born adult monkeys. Juvenile male monkeys born to feral mothers in the lab were either exposed to a live snake during infancy or were snake-naive. Simultaneously tested were adult feral-born and adult lab-born (snake-naive) males. Juveniles exposed as infants to a snake displayed behavioral responses and plasma cortisol elevations following exposure to the snake that were similar to those of feral-born adults. In contrast, the snake-naive monkeys, regardless of age, rarely vocalized at the snake and displayed lower plasma cortisol elevations. These behavioral and physiological responses did not appear to be elicited by a moving animate stimulus per se, insofar as exposure to a moving fish elicited minimal behavioral changes and no cortisol elevations. In contrast to previous findings, these studies indicate that lab-born snake-naive squirrel monkeys are responsive to snakes, but that experience with snakes in infancy produces behavioral and physiological responses more similar to those observed in feral-born monkeys.

Temporal and social factors influencing behavioral and hormonal responses to separation in mother and infant squirrel monkeys.

The behavioral and hormonal responses of mother and infant squirrel monkeys (Saimiri sciureus) were examined to assess temporal and environmental factors that influence the response to separation. In two experiments evaluating the effects of 1-, 3-, 6-, and 24-hr separations, it was found that signs of infant behavioral agitation decreased over time, whereas adrenocortical activation persisted or even increased. Moreover, two separation environments were shown to differentially affect behavioral and hormonal responses. Separated infants vocalized significantly more when their mothers were proximal than when isolated, but showed lower cortisol levels in the adjacent separation than in the total-isolation condition. These data indicate that the intensity of the infant's calling response cannot be used to predict internal state (as reflected by cortisol levels). Furthermore, vocalization rate is highly dependent upon contingent stimuli, such as the presence of maternal cues. Following separation, the mothers also showed elevated cortisol levels. However, both the magnitude and pattern of the response differed considerably from that of the infant.

Behavioral and physiological responses of mother and infant squirrel monkeys to fearful stimuli.

The behavioral and adrenocortical responses of feral squirrel monkey mothers and their laboratory-born infants were measured following exposure to a live snake and to a flying predator model (hawk). The dyads were either socially or individually housed. The different stimuli were presented above the home cage for 1 hr; behaviors were observed during this period. Blood samples were obtained at the end of the test session and assayed for cortisol. The results indicated that individually housed dyads markedly increased their time spent in contact and their avoidance of the stimuli, and showed increased levels of cortisol when exposed to the snake or hawk model. Socially reared monkeys responded only to the snake. Thus, the presence of social partners ameliorated the response to the hawk model. The marked increase in contact during the presentation of the fear-eliciting stimuli may be partly responsible for the infants' response.

Time course of the effect of maternal deprivation on the hypothalamic-pituitary-adrenal axis in the infant rat.

Prolonged (i.e., 24-hr) maternal deprivation leads to a marked disinhibition of the infant rat's adrenocortical response to stress and/or ACTH. In the following study we examined the time course over which these effects develop. Pups were maternally deprived for varying lengths of time (i.e., 0, 2, 4, 8, & 24 hr); at the end of this period, corticosterone (CORT) secretion in response to stress (novelty or novelty plus saline injection) and ACTH injection was measured. Basal levels of CORT increased progressively over time in 7- and 11- (but not 3-) day-old pups. CORT release in response to stress followed a similar pattern. In contrast, ACTH injection resulted in marked increases in CORT levels regardless of the length of maternal deprivation in 3-day-old animals; at older ages, however, 24 hr of deprivation led to a much larger increase. These findings support the hypothesis that the hypothalamic-pituitary-adrenal axis of the neonatal rat is subject to maternal regulation.

Passage of MHPG from plasma to CSF in a non-human primate.

In experimental protocols with humans and non-human primates, cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the predominant end-product of norepinephrine metabolism in the mammalian central nervous system (CNS), have been widely used as an index of the rate of CNS norepinephrine metabolism. However, an earlier investigation showed that there was slow but free exchange between plasma and CSF MHPG. To define more precisely the time-course of equilibration of plasma and CSF MHPG, we intravenously administered 100 micrograms/kg of [2H3]-MHPG to drug-naive squirrel monkeys. Measurements were made of the concentrations of [2H3]- and [1H]-MHPG in plasma and cervical CSF samples collected at time points from 10 min to 4 hr thereafter. The results indicated that neither plasma nor CSF concentrations of [1H]-MHPG changed during the course of the experiment, and that [2H3]-MHPG appeared in the CSF within 10 min of intravenous administration. The maximal plasma and CSF concentrations of [2H3]-MHPG were 7.6- and 2.3-fold higher than the respective concentrations of [1H]-MHPG. The plasma and CSF pools of [2H3]-MHPG reached concentration equilibrium within 30 min, and thereafter the temporal decline in concentration of [2H3]-MHPG was the same in plasma and CSF. These results demonstrate that MHPG rapidly crosses from plasma to CSF, and support the suggestion that this factor be included in any attempts to estimate norepinephrine turnover in the CNS from measurements of steady-state MHPG concentrations in CSF or plasma.

Behavioral and physiological responses to maternal separation in squirrel monkeys (Saimiri sciureus).

This study extends an examination of the behavioral and pituitary-adrenal responses of infant squirrel monkeys (Saimiri sciureus) separated from their mothers under different environmental conditions to another physiological system by measuring the metabolites of the central monoamines found in the cerebrospinal fluid (CSF). This study included spectrographic examination of the vocalizations emitted by the infant during separation. Infants were separated from their mothers for 24 hr under 3 conditions: Home, infant remained in its home cage after removal of mother; adjacent, infant was placed in a cage adjacent to its mother; and total, infant was totally isolated. The behavioral results indicated that the number of calls emitted differed with condition (adjacent greater than total greater than home), and the peak frequency of the calls and number of multiple calls was greatest in the total condition. Plasma cortisol elevations after separation differentiated the conditions of separation (total greater than adjacent greater than home greater than base). The elevations in the CSF catecholamine metabolites (3-methoxy-4-hydroxyphenylglycol and homovanillic acid) were also sensitive to the conditions of separation (total greater than adjacent greater than base). These results are discussed in the context of coping theory.

Allergic contact dermatitis to nasturtium.

In conclusion, oil of mustard, contained in many plants and recognized mainly as a skin irritant, is also capable of causing an allergic contact dermatitis. Nasturtium, which contains mustard oil, should be added to the list of plants capable of causing this dermatitis and must be suspected in any patient who handles plants and presents with hand dermatitis.

5-Hydroxyindoleacetic acid in cerebrospinal fluid reflects serotonergic damage induced by 3,4-methylenedioxymethamphetamine in CNS of non-human primates.

This study examined whether 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) could be used to detect serotonergic damage induced by (+/-)-3,4-methylenedioxymethamphetamine (MDMA) in the central nervous system (CNS) of non-human primates. Monkeys were administered toxic doses of MDMA; two weeks later, the animals were lightly anesthetized with ether and CSF was obtained by means of cervical puncture. Later that same day, the animals were killed for direct determination of CNS serotonin and 5-HIAA concentrations. Monkeys with 73-94% depletions of serotonin and 5-HIAA in brain and 42-45% depletions of serotonin and 5-HIAA in the spinal cord had a 60 +/- 7% reduction of 5-HIAA in CSF, without any change in homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenethyleneglycol (MHPG). These findings indicate that CSF 5-HIAA can be employed to detect central serotonergic damage produced by MDMA in non-human primates, and suggest that CSF 5-HIAA may be useful for detecting MDMA-induced neuronal damage in humans.

Psychoendocrine aspects of mother-infant relationships in nonhuman primates.

Studies will be presented which examine the physiological and behavioral responses of squirrel monkeys and rhesus macaques following disruptions of mother-infant relationships. Reliable increases in circulating levels of plasma cortisol occur following separation of the infant from its mother. The presence of familiar conspecifics during the time of separation reduces the pituitary-adrenal response, compared to that elicited by total isolation. Visual access to the mother during separation also ameliorates the plasma cortisol response. However, when infants are separated in the presence of unfamiliar conspecifics, the physiological response is exaggerated compared to animals which are totally isolated. The behavior expressed by the infant during separation, particularly separation-induced vocalizations, is not concordant with this physiological index of affect. The rate of vocalization produced when the infant has visual access to the mother was higher than when the infant was totally isolated. However, when allowed access to familiar conspecifics, the rate of vocalization was lower than during total isolation, with no vocalization produced while the separated infant was in the unfamiliar social group. The curvilinear relationship between vocalization and the physiological index of arousal has led to a revision of the traditional concept that separation-induced infant vocalization is reflective of distress. These data support the hypothesis that vocalizations may serve as a coping response that reduces the physiological indices of arousal. Social interaction with familiar cospecifics may serve as a non-vocal coping response (e.g., proximity contact to other monkeys) which also reduces the behavioral and physiological responses to maternal separation.

Primate vocalization: a psychobiological approach.

Scientific inquiry, for the most part, can be described as parochial. Not only are there clear demarcations between broad disciplinary categories (i.e., anatomy, physiology, psychology), but subspecialties are common within disciplines. Modern technology has made possible a trend toward greater and greater specialization. In fact, there are now areas of scientific investigation that did not exist a few years ago. This increasing specialization and its concomitant reductionism is not without its pitfalls and problems. There is a tendency to move away from the basic evolutionary concept of living organisms as organized systems functioning and adapting within an ecosystem. The laboratory scientist often ignores the inherent organization of living systems in favor of an intense pursuit of his or her particular chosen bit of the biological puzzle. However, there are still disciplines that not only subscribe to the notion of living organisms as organized systems but have made a valiant attempt to bring this concept under laboratory scrutiny. Often, in order to identify these endeavors, a technique is used to combine two or three words into one. Thus, we have several flourishing disciplines described as psychoneuroimmunology, psychoneuroendocrinology, neurochemistry, physiosociology, and so on. For the investigator who attempts a more integrated approach to the broad biological and psychological universe, the demands are heavy. He or she is faced with the need to maintain credibility in several disciplines, each of which is advancing at an accelerated pace. However, we feel that the value of an integrated approach that crosses traditional disciplinary lines will be illustrated in a small way by this article and, we hope, by the series of articles presented in this symposium section of Child Development.

Influence of postnatal rearing conditions on the response of squirrel monkey infants to brief perturbations in mother-infant relationships.

This study was designed to determine the behavioral and pituitary-adrenal responses of squirrel monkey mother-infant dyads reared under different housing conditions to either 1- or 6-hr separations. Dyads were reared either in an individual cage or in social groups of 3 mother-infant dyads. The two separation conditions consisted of removing either the mother or the infant to a novel test cage while the other member remained in the home cage. Group-reared infants displayed lower levels of plasma cortisol, movement, and vocalization when they remained in the home cage during separation compared to their responses in the novel cage. However, individually-reared infants displayed high cortisol and activity levels in both separation environments, and vocalization levels were higher at 1 hr in the home cage than in the novel cage. These results indicate that familiarity with the separation environment, per se, does not attenuate the behavioral or physiological responses of infants, but that familiar conspecifics, even in the absence of alloparenting, can benefit an infant during separation from its mother. Two additional test conditions assessed the responses of mother-infant dyads when they were only momentarily separated and then immediately reunited in either the home cage or a novel cage. Reunion in the home cage evoked no cortisol or behavioral responses, but reunion in a novel cage resulted in significant elevations in infant cortisol levels and time in contact with the mother. The corticoid response of the mothers differed from their infants during separations.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid cortisol and corticosteroid-binding globulin responses during pregnancy and after estrogen administration in the squirrel monkey.

Plasma cortisol and corticosteroid-binding globulin (CBG) levels were assessed in pregnant squirrel monkeys and in intact and castrated males after estrogen administration. Pregnant females showed a rapid and dramatic rise in cortisol and CBG during the first 8 weeks after conception. Estrogen treatment also caused marked elevations in cortisol and CBG. Cortisol levels increased significantly by 24 h after estrogen injection and remained elevated for 6 weeks of treatment, but a relatively greater rise in CBG resulted in a higher CBG/cortisol ratio. The data support prior research indicating that estrogen can simultaneously stimulate adrenal output and the compensatory binding of circulating cortisol by increased CBG synthesis. In addition, it appears that even in the absence of exogenous treatment, the pituitary-adrenal axis of male squirrel monkeys is stimulated by estrogen derived either from the testes or by the peripheral conversion of testosterone to estrogen.

Endocrine response to acute cold exposure by lactating and non-lactating Norway rats.

Plasma levels of corticosterone, prolactin and thyroxine (T4) were measured in lactating and non-lactating Norway rats at 22 degrees C and 4 degrees C. Acute cold exposure increased corticosterone secretion in all groups, although non-lactating female levels rose higher than those of mother rats. While prolactin levels are unaffected by acute cold exposure in non-lactating females, mothers with their litters had lower prolactin levels in the cold. T4 levels increased during cold exposure in lactating females, suggesting that the low T4 levels observed during lactation may not be due to lactational competition for available iodine.

ACTH and corticosterone secretion in rats following removal of the neurointermediate lobe of the pituitary gland.

Surgical removal of the neurointermediate lobe of the pituitary gland (NIL-X) in the rat resulted in two abnormalities in ACTH secretion: (1) plasma ACTH and corticosterone levels were elevated in the morning and over a 24-hour period compared with levels in control (NIL-C) rats, and (2) although NIL-X and NIL-C rats had acute increases in plasma ACTH and corticosterone of equal magnitude after interoceptive stimuli (hemorrhage, surgery), NIL-X rats demonstrated markedly smaller elevations in plasma levels of these hormones after neurotropic stimuli (noise, novel environment). This subnormal adrenocortical response of NIL-X rats was not due to an impairment in perception of a neurotropic stimulus; these rats had normal latencies to paw licking and to jumping off a heated surface, yet smaller increases in plasma corticosterone after the stimulus. The impairment in ACTH response was not related to stimulus intensity, as NIL-X and NIL-C rats had equal ACTH and corticosterone secretion during both low and high levels of insulin-induced hypoglycemia. NIL-X rats demonstrated a significant elevation in daily water intake, although hematocrit, plasma Na+, K+, osmolality and protein were normal. Significant diurnal rhythms in plasma corticosterone levels and in water intake were maintained as well. The elevated morning plasma ACTH levels, the blunted hormone increases after noise, and the increase in water intake persisted in NIL-X rats 2 months after surgery. These data indicate that removal of the NIL results in (1) chronic elevations in basal ACTH and corticosterone secretion, and (2) chronic impairment in adrenocortical responses to neurotropic stimuli, but not to interoceptive stimuli. The deficit is not due to impaired perceptual capacity nor to the intensity of the stimulus.

Influence of perinatal malnutrition and early handling on the pituitary-adrenal response to noxious stimuli in adult rats.

A series of experiments examined the influence of perinatal malnutrition and infantile stimulation (preweaning handling) on the pituitary-adrenal response to novelty, electric shock and ether in adult rats. Neither early experience variable altered the magnitude or time course of the plasma corticosterone response to the combined stress of ether exposure and cardiac puncture. Although perinatal malnutrition did not change the magnitude of the adrenocortical response 15 min following a 1-min exposure to a novel test chamber alone or with 0.25 or 1.0 mA of scrambled electric shock, early handled subjects of both nutrition groups displayed lower corticoid elevations compared to nonhandled rats. Additionally, all subjects showed a lower corticoid elevation to the novel chamber without shock compared to the chamber plus electric shock, with females being able to display a differential corticoid response to the two shock levels. Perinatal malnutrition did not alter the magnitude and time course of the ACTH response to a 1-min exposure to a novel chamber alone or with ether. Thus, perinatal malnutrition does not appear to alter either the basal levels of ACTH and corticosterone or the response of these hormones following the stressors examined. Early handling modulated the response to novelty and electric shock but not ether, suggesting that the latter response is mediated by brain regions not influenced by infantile stimulation. Finally, the results of these studies indicate that the magnitude of the pituitary-adrenal response reflects different intensity levels of electric shock in female rats.

Influence of perinatal malnutrition on adult physiological and behavioral reactivity in rats.

A series of experiments examined the behavioral and pituitary-adrenal response to novelty of perinatally malnourished rats tested as adults after nutritional rehabilitation begun at weaning. Neither the behavioral measures of ambulation, rearing and defecation, nor the plasma corticosterone response to a brief exposure to an open field differentiated the previously malnourished subjects from controls. Similar to controls, previously malnourished subjects were also capable of displaying a graded corticoid elevation to environments increasingly different from the home cage. However, exploratory behavior, as measured by head-dip frequency and duration in the hole-board, was reduced in the previously malnourished rats. Although latency and amount of fluid consumed in a novel environment did not differ, previously malnourished rats were unable to use the cues associated with a consummatory behavior to modulate the pituitary-adrenal response to novelty. Thus, perinatal malnutrition does not influence either the behavioral or physiological activational response to novel stimulation but appears to alter the ability of the animal to use a consummatory behavior to modulate this response.

Behavioral, but not physiological, adaptation to repeated separation in mother and infant primates.

Mother and infant squirrel monkeys were subjected to a series of brief separations in order to evaluate how behavioral and physiological responses change following multiple exposures to stress. Beginning when the infants reached three months of age, their behavioral and hormonal responses were assessed during six 1-hr separations; and additional five dyads served as controls for the effect of repeated disturbance. The separated infants showed a marked and progressive decrease in distress calling across time, but no change was observed in the high levels of agitated activity or the plasma cortisol response to separation. This finding questions the traditional use of distress vocalizations as a measure of stress and indicates that certain types of behavior can change independently of physiological arousal responses, which may continue to occur even after repeated exposures to stress.

Injectable sodium chloride as a local anesthetic for skin surgery.

Sodium chloride injected intracutaneously has proved to be an effective local anesthetic for superficial skin surgery. Among the advantages of sodium chloride over the "caines" are: absence of burning or stinging on injection, lack of sensitization, and lower cost. Lesions can be removed by the parallel scalpel technique, razor technique, or curettage. Saline also provides adequate anesthesia for punch biopsies and electrocautery techniques. Lesions removed to date have been numerous--nevi, papillomas, and verrucas. Biopsies of benign and malignant lesions have also been performed with this technique.