Search PubMed⌕ Search

Biomedical subjects

N H Kalin

Publications and source records attributed to N H Kalin.

At least 55 records · Page 3Linked to original sources

Prenatal stress potentiates stress-induced behavior and reduces the propensity to play in juvenile rats.

We examined the hypothesis that prenatal stress potentiates defensive responsiveness which may interfere with the expression of appetitive behavioral activities. Sibling pairs of prenatally stressed and control juvenile rats were placed in an unfamiliar environment. The latency and frequency of social play, a sought-after activity of juvenile rats, were measured on 4 successive days beginning at 25 days of age. However, on Day 27, electric foot shock was administered in order to assess directly whether exposure to threat facilitates the occurrence of defensive behavior in prenatally stressed rats. In addition, to determine whether previous exposure to threat produces long-term suppressive effects on play, rats were retested on Day 28 in the absence of shock. Throughout the testing period, the latency to play, as indicated by one rat pouncing on the opponent, was significantly higher in prenatally stressed than control rats. The frequency of play, however, did not differ reliably between groups. These data suggest that prenatally stressed rats take longer to adapt to the test situation before initiating play than control rats. In both groups, exposure to shock on Day 27 significantly increased the latency to play. More importantly, prenatally stressed rats exhibited significantly higher durations of defensive freezing than control animals. When retested on Day 28, however, the duration of freezing declined significantly and no longer differed between groups. Data appear to support the hypothesis that prenatally stressed juvenile rats are responsive to stress which may modulate the inclination to exhibit social behavior.

Adrenocorticotropic Hormone↗

Affiliative vocalizations in infant rhesus macaques (Macaca mulatta).

In Experiment 1, infant rhesus monkeys (Macaca mulatta) were separated and then reunited with mothers, united with a male, or placed in an empty cage. Infants girned more when with mothers or the male than when alone. Girns declined over time when infants were united with the male. Coo rates were high when the infant was alone or with the male. Shrieks, barks, and fear-related behavior were higher with the male. In Experiment 2 the vocalizations of infants were examined during separation when alone or when mothers or a male were in the same room. Infants cooed more when mothers or a male were present. Cooing increased over time, with a greater increase in the mothers' presence. Girns were given to both mothers and males, but more were given to mothers. Coos and girns are both affiliative vocalizations but are differentially modulated as infants cease cooing when they receive contact comfort.

Animal Communication↗

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers. Of the indices of LHPA activity, only CSF CRF concentrations distinguished the four subject groups, with CSF CRF being significantly elevated in the more severely depressed major depression patients. Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers. These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity, at least as determined cross-sectionally. Further longitudinal studies with reference to diagnostic subtypes, severity, symptom profiles, and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations.

Adrenocorticotropic Hormone↗

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

Adrenal Cortex Hormones↗

Development of stress-induced responses in preweanling rats.

This study examined in postnatal Days 7, 14, and 21 male rats the effects of social isolation and social isolation with administration of brief foot shocks on the development of stress-induced behavioral and pituitary-adrenal hormone responses. Day 21 rats appeared similar to adult rats in their repsonses to the two test conditions. That is, exposure to either isolation or to shock increased both pituitary-adrenal hormone secretion and tail-flick latencies but only administration of shock potentiated freezing and ultrasonic vocalizations. Younger rats differed from Day 21 rats in their responses to the two test conditions. In both tests, Day 7 rats produced the highest number of ultrasounds, which may be due to a significant decrease in body temperature. In contrast, in Day 14 pups, exposure to shock significantly reduced isolation-induced ultrasonic vocalizations. Additional age-dependent differences were found in the analgesic responses of Days 7 and 14 rats. Day 7 rats exposed to stress became consistently hyperalgesic whereas Day 14 rats showed only a short-lasting analgesic response. Although in Days 7 and 14 rats exposure to the two stress conditions produced significant elevations in pituitary-adrenal hormone concentrations, plasma levels were lower than those measured in Day 21 rats. To summarize, preweanling rats exhibit varied age-dependent responses when exposed to different stress environments.

Adrenocorticotropic Hormone↗

Effects of alprazolam on fear-related behavioral, hormonal, and catecholamine responses in infant rhesus monkeys.

We tested the effects of various doses of the triazolobenzodiazepine alprazolam on behavioral, hormonal, and neurochemical responses of infant rhesus monkeys under three conditions of separation from their mothers: alone, in the presence of a human who stared at them, and in the presence of a human who avoided eye contact. Alprazolam affected stress-induced responses in all three of these classes. Unrelated to its effects on the stress response, alprazolam appears to reduce the function of brain dopamine systems.

Adrenocorticotropic Hormone↗

Air travel across four time zones in college swimmers.

Eighteen female and 22 male college swimmers were flown across four time zones in east-to-west (E-W) and west-to-east (W-E) directions. A pre- and postflight paced swim of 182.9 m at an intensity equal to 90% of the swimmers' maximal velocity was completed, and salivary cortisol, heart rate (HR), and rated perceived exertion were measured. Blood pressure, HR, muscle soreness, and mood were also assessed at rest on the day before and on the day after travel. Because training volumes for both females and males were greater (P less than 0.001) in the week before W-E than E-W travel, the W-E and E-W data were analyzed separately. Two-way repeated-measures analyses of variance revealed that pre- and postexercise cortisol decreased after E-W travel and increased after W-E travel in comparison to preflight values. Resting and exercise HR responses to air travel were small in magnitude, and their significance depended on the direction of travel. Effort sense was not altered by air travel, but significant (P less than 0.001) improvements in mood and reductions in muscle soreness were observed after E-W and W-E travel for both genders. It was concluded that 1) female and male college swimmers have similar responses to air travel and 2) air travel across four time zones during heavy swim training does not have negative physiological, perceptual, or affective consequences.

Adolescent↗

Defensive behaviors in infant rhesus monkeys: ontogeny and context-dependent selective expression.

We examined the ontogeny of the infant rhesus monkey's defensive behaviors and the ability to modulate them in response to specific environmental cues. Rhesus infants in 4 age groups (N = 8 per group) were briefly separated from their mothers and tested under 3 conditions: alone, in the presence of a human who averted his gaze, and in the presence of a human staring at them. Infants as young as 0 to 2 weeks displayed defensive behaviors but did not selectively respond to the human's presence or direction of gaze. By 9 to 12 weeks of age, infants modulated their responses in relation to the parameters of the threat. At this age, infant rhesus monkeys undergo cognitive and emotional changes associated with brain development similar to those in human infants 7 to 12 months old. This also is the time when human infants engage in complex emotional and behavioral responses to threatening situations. Understanding the development and expression of defensive behaviors in infant monkeys should be applicable to similar issues in emotional development of human infants.

Aging↗

Fear-motivated behavior induced by prior shock experience is mediated by corticotropin-releasing hormone systems.

In earlier studies, we established that in rats, antagonism of corticotropin-releasing hormone (CRH) receptors reduced the occurrence of fear-motivated behavior displayed immediately after administration of electric foot shock. Because exposure to stress is reported to have long-term behavioral and physiological effects, we examined whether central administration of the synthetic CRH receptor antagonist, alpha-helical CRH(9-41), would also alter fear-motivated behavioral and hormonal responses occurring 24 h after exposure to electric foot shock. Adult male rats were placed in a shock box and administered three, 1.0 mA foot shocks. Twenty-four hours later, rats received an intracerebroventricular infusion of 20 micrograms of alpha-helical CRH(9-41) or vehicle 20 min before re-exposure to the shock box. Antagonism of CRH receptors produced a significant reduction in fear-motivated freezing. However, stress-induced analgesia and plasma adrenocorticotropin concentrations did not differ significantly from vehicle-treated animals. In order to assess whether the reduction in freezing was due to intrinsic actions of the CRH receptor antagonist, non-shocked rats received central infusions of alpha-helical CRH(9-41) prior to re-exposure to the test box. Under these conditions, behavior exhibited by antagonist- and vehicle-treated rats did not differ significantly. Results suggest that the reduction in fear-motivated behavior is mediated by antagonism of endogenous CRH receptors and occurs independently of analgesic and hormonal reactions induced by prior exposure to stress.

Adrenocorticotropic Hormone↗

Ontogeny of behavioral and hormonal responses to stress in prenatally stressed male rat pups.

Effects of prenatal stress on stress-induced behavioral and hormonal responses were investigated in preweanling rats at two ages. Prenatal stress treatments involved the application of uncontrollable electric shocks to pregnant rats every other day throughout gestation. Offspring of undisturbed rats in home cages served as controls. When male pups were 14 and 21 days old, ultrasonic vocalizations and freezing were recorded in 10-min tests involving isolation, and isolation with the application of electric foot shocks at either 0.5- or 2.0-mA intensity. Immediately before and after each test, tail-flick latencies were measured in order to assess alterations in stress-induced analgesia. Stress-induced secretion of ACTH was measured in plasma obtained after the second tail-flick test. Results indicated that 14-day-old prenatally stressed pups emitted significantly fewer ultrasonic vocalizations and exhibited significantly lower percent increases in tail-flick latencies than control pups. Plasma ACTH, however, was significantly elevated in prenatally stressed rats, suggesting that exposure to different tests was a stress-inducing event. At 21 days of age, prenatally stressed rats no longer differed significantly from control males in the exhibition of ultrasonic vocalizations, defensive freezing, and tail-flick latencies. Plasma ACTH content, however, was significantly lower in prenatally stressed than control males after exposure to the isolation with 2.0-mA shock test. The involvement of motivational, maturational, and mediational factors is examined in order to account for these age-dependent and stressor-dependent differences in behavioral and hormonal responses occurring between prenatally stressed and control pups.

Adrenocorticotropic Hormone↗

Corticotropin-releasing factor antagonist attenuates defensive-withdrawal behavior elicited by odors of stressed conspecifics.

This study examined the hypothesis that defensive responsiveness induced by threatening stimuli of biological origin is mediated by the action of endogenous corticotropin-releasing factor (CRF). Rats were exposed for 15 min to a large open field containing a small chamber. Twenty-four hours later, rats received intracerebroventricular injections of either vehicle or 20 micrograms of alpha-helical CRF(9-41), a CRF receptor antagonist. After 20 min, rats were reexposed to the open field, which now contained odors of urine and feces from a stressed conspecific. In the reexposure test, vehicle- and antagonist-treated rats withdrew rapidly into the chamber. Antagonist-treated rats, however, emerged subsequently from the chamber to explore the open field as indicated by a significant increase in the number of passages made between the chamber and the open field. Results suggest that central injection of alpha-helical CRF(9-41) reduces the level of fear induced by odors associated with threat. In addition, CRF receptors are implicated in mediating the species-typical display of defensive-withdrawal behavior.

Animals↗

Defensive behaviors in infant rhesus monkeys: environmental cues and neurochemical regulation.

To survive, primates must detect danger in time to activate appropriate defensive behaviors. In this study, the defensive behaviors of infant rhesus monkeys exposed to humans were characterized. It was observed that the direction of the human's gaze is a potent cue for the infant. Infants separated from their mothers were active and emitted frequent distress vocalizations. When a human entered the room but did not look at the infant, it became silent and froze in one position. If the human stared at the infant, it responded with aggressive barking. Alterations of the opiate system affected the frequency of the infant's distress calls without affecting barking and freezing, whereas benzodiazepine administration selectively reduced barking and freezing. This suggests that opiate and benzodiazepine systems regulate specific defensive behaviors in primates and that these systems work together to mediate behavioral responses important for survival.

Aggression↗

Mood state and salivary cortisol levels following overtraining in female swimmers.

Mood, as measured by the Profile of Mood States questionnaire, and resting salivary cortisol levels were examined in 14 female college swimmers during progressive increases and decreases in training volume, and were compared to the same measures in eight active college women who served as controls. Training volume increased from 2,000 yards/day in September (baseline) to a peak of 12,000 yards/day in January (overtraining), followed by a reduction in training (taper) to 4,500 yards/day by February. The swimmers experienced significant (p less than 0.01) alterations in tension, depression, anger, vigor, fatigue and global mood across the training season compared to the controls. Salivary cortisol was significantly (p less than 0.01) greater in the swimmers compared to the controls during baseline and overtraining, but was not different between the groups following the taper. Salivary cortisol was significantly correlated with depressed mood during overtraining (r = .50; p less than 0.05) but not at baseline or taper. Global mood, depression, and salivary cortisol were significantly (p less than 0.05) higher during the overtraining phase in those swimmers classified as stale, compared to those swimmers who did not exhibit large performance decrements.

Affect↗

Behavioral and physiologic effects of CRH administered to infant primates undergoing maternal separation.

Infant rhesus monkeys briefly separated from their mothers emit frequent distress vocalizations and alter their activity levels. These behavioral alterations are accompanied by physiologic changes and activation of the hypothalamic-pituitary-adrenal axis. Because corticotropin-releasing hormone (CRH) is a major regulator of the pituitary-adrenal system and has been implicated as a mediator of other aspects of the stress response, we examined the effects of centrally and peripherally administered CRH on the infant monkey's separation response. Intracerebroventricular (ICV) doses less than 10 micrograms did not alter behavior; 10-micrograms doses inhibited behavior without affecting distress vocalizations. The behavioral inhibition did not appear to be due to nonspecific sedation and may be related to increased fearfulness. It was accompanied by increases in adrenocorticotropic hormone (ACTH) and cortisol and small but significant decreases in body temperature and mean arterial pressure. Within an individual animal, no relationship was seen between ICV CRH's effects on physiologic parameters and its effects on behavior. ICV CRH produced significant increases in plasma concentrations of CRH, suggesting the possibility that the effects of CRH were mediated through peripheral mechanisms. However, 10 micrograms of CRH administered intravenously (IV) had no effect on behavior, blood pressure, or body temperature, nor did it increase plasma concentrations of ACTH or cortisol beyond the expected separation-induced elevation. This is interesting because plasma levels of CRH after IV CRH were much greater than after ICV CRH. Our findings suggest that in infant rhesus monkeys undergoing maternal separation, brain CRH systems mediate behavioral inhibition and pituitary-adrenal activation.

Adrenocorticotropic Hormone↗

Corticotropin-releasing factor modulates defensive-withdrawal and exploratory behavior in rats.

The role of corticotropin-releasing factor (CRF), an endogenous neuropeptide, in modulating species-typical responses was examined in an unfamiliar open field containing a small chamber. Rats placed in this small chamber spent most of their time withdrawn in it. However, rats given an intracerebroventricular injection (20 micrograms) of alpha-helical CRF(9-41), a CRF receptor antagonist, emerged from the chamber and explored the unfamiliar open field. Additional studies showed that after 1 exposure to the test environment, vehicle-treated rats increased their time spent in the open field and returned intermittently to the chamber. This result suggests that reexposure reduces the threatening impact of an unfamiliar open field. Importantly, CRF (300 ng) injected centrally, but not peripherally, before reexposure to the test environment significantly reduced exploration in the open field and increased a pattern of defensive-withdrawal into the chamber. Data suggest that whether defensive-withdrawal or exploratory behavior is exhibited may depend on CRF actions in brain systems that mediate the perception of threat in the environment.

Animals↗

Antagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats.

Three experiments were conducted to test the hypothesis that brain corticotropin-releasing hormone (CRH) systems mediate stress-induced freezing behavior, an index of a rat's level of fear. We administered i.c.v. 0-50 micrograms of alpha-helical CRH9-41 (a specific CRH antagonist) before foot shock and showed that this peptide had little effect on baseline preshock behavior but significantly attenuated the occurrence of shock-induced freezing. We concluded that this attenuation of freezing behavior was not related to the effects of alpha-helical CRH9-41 on the animals' sensitivity to pain, because no significant effects on latency to respond on a hot-plate test of pain sensitivity were found. We also showed that alpha-helical CRH9-41 has a relatively rapid time course of action when administered i.c.v., since it blocked shock-induced freezing when given 20 min but not 40 min before foot shock. Our findings suggest that endogenous CRH systems mediate stress-induced, fear-related behavior through mechanisms other than alteration of nociceptive systems.

Animals↗