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Biomedical subjects

N H Kalin

Publications and source records attributed to N H Kalin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Individual differences in freezing and cortisol in infant and mother rhesus monkeys.

Freezing is an adaptive defensive behavior that is expressed in response to an imminent threat. In prior studies with rhesus monkeys, stable individual differences in animals' propensities to freeze have been demonstrated. To understand the factors associated with these individual differences, freezing behavior was examined in infant rhesus monkeys and their mothers, in conjunction with levels of the stress-related hormone cortisol. In both mothers and infants, basal cortisol levels were positively correlated with freezing duration. Additionally, the number of offspring a mother had was negatively correlated with her infant's cortisol level. These findings suggest a link between basal cortisol levels and an animal's propensity to freeze, as well as a mechanism by which maternal experience may affect infants' cortisol levels.

Animals↗
PubMed1998

Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys.

The authors examined the hypothesis that rhesus monkeys with extreme right frontal electroencephalographic activity would have higher cortisol levels and would be more fearful compared with monkeys with extreme left frontal activity. The authors first showed that individual differences in asymmetric frontal electrical activity are a stable characteristic. Next, the authors demonstrated that relative right asymmetric frontal activity and cortisol levels are correlated in animals 1 year of age. Additionally, extreme right frontal animals had elevated cortisol concentrations and more intense defensive responses. At 3 years of age, extreme right frontal animals continued to have elevated cortisol concentrations. These findings demonstrate important relations among extreme asymmetric frontal electrical activity, cortisol levels, and trait-like fear-related behaviors in young rhesus monkeys.

Agonistic Behavior↗
PubMed1997

Microinfusion of corticotropin-releasing factor into the nucleus accumbens shell results in increased behavioral arousal and oral motor activity.

Corticotropin-releasing factor (CRF) is a 41 amino acid peptide postulated to be involved in integrating the physiological and behavioral responses to stress. The purpose of this experiment was to determine the effects of CRF microinfused into the nucleus accumbens core (AcbC) and shell (AcbSh) subregions. Rats were tested for general motor activity, cage crossings, and rearing following CRF (0, 125, 250, or 500 ng). Behavioral observations were also made to determine the profile of activity caused by CRF infusion into the Acb. CRF in the AcbSh but not the AcbC regions elicited an increase in general motor activity that lasted approximately 2 h. When compared with ventricular injections, CRF in the AcbSh had greater activating effects. The CRF-induced behavioral profile consisted of increases in grooming, sniffing, and oral behavior. Results are discussed as they pertain to the involvement of the AcbSh in stress, motivated behavior, and drug sensitization.

Animals↗
PubMed1997

Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine.

BACKGROUND: Functional magnetic resonance imaging (fMRI) techniques were used to identify the neural circuitry underlying emotional processing in control and depressed subjects. Depressed subjects were studied before and after treatment with venlafaxine. This new technique provides a method to noninvasively image regional brain function with unprecedented spatial and temporal resolution. METHOD: Echo-planar imaging was used to acquire whole brain images while subjects viewed positively and negatively valenced visual stimuli. Two control subjects and two depressed subjects who met DSM-IV criteria for major depression were scanned at baseline and 2 weeks later. Depressed subjects were treated with venlafaxine after the baseline scan. RESULTS: Preliminary results from this ongoing study revealed three interesting trends in the data. Both depressed patients demonstrated considerable symptomatic improvement at the time of the second scan. Across control and depressed subjects, the negative compared with the positive pictures elicited greater global activation. In both groups, activation induced by the negative pictures decreased from the baseline scan to the 2-week scan. This decrease in activation was also present in the control subjects when they were exposed to the positive pictures. In contrast, when the depressed subjects were presented with the positive pictures they showed no activation at baseline, whereas after 2 weeks of treatment an area of activation emerged in right secondary visual cortex. CONCLUSION: While preliminary, these results demonstrate the power of using fMRI to study emotional processes in normal and depressed subjects and to examine mechanisms of action of antidepressant drugs.

Adolescent↗
PubMed1996

A new method for aversive Pavlovian conditioning of heart rate in rhesus monkeys.

Aversive Pavlovian conditioning is an important tool used to investigate neurobiological mechanisms underlying the acquisition and expression of fear. Most studies have used nonprimate species employing electrical shock as the unconditioned stimulus (US). Although important advances have been made in understanding the neural substrates of conditioned fear, the extent to which these findings apply to primates is unclear. Research in primates has not progressed because of the lack of a conditioning paradigm that does not use shock. Therefore, we developed a method that uses a US consisting of a loud noise coupled with a stream of compressed air aimed at the face to aversively condition heart rate response in rhesus monkeys. With this US, rhesus monkeys rapidly acquire a conditioned bradycardia. The availability of an easy, reliable, and efficient method of aversive conditioning that does not require electrical shock, will facilitate studies investigating neurobiological mechanisms underlying the acquisition and expression of fear in primates.

Animals↗
PubMed1996

Individual differences in repressive-defensiveness predict basal salivary cortisol levels.

Prior studies assessing the relation between negative affective traits and cortisol have yielded inconsistent results. Two studies assessed the relation between individual differences in repressive-defensiveness and basal salivary cortisol levels. Experiment 1 assessed midafternoon salivary cortisol levels in men classified as repressors, high-anxious, or low-anxious. In Experiment 2, more rigorous controls were applied as salivary cortisol levels in women and men were assessed at 3 times of day on 3 separate days. In both studies, as hypothesized, repressors and high-anxious participants demonstrated higher basal cortisol levels than low-anxious participants. These findings suggest that both heightened distress and the inhibition of distress may be independently linked to relative elevations in cortisol. Also discussed is the possible mediational role of individual differences in responsivity to, or mobilization for, uncertainty or change.

Adolescent↗
PubMed1995

Opiate systems in mother and infant primates coordinate intimate contact during reunion.

In humans, and non-human primates, reunion following a separation results in a positive emotional state, and an increase in affiliative behaviors. To examine the role of opiate systems, in mothers and infants in mediating reunion behavior, morphine and naltrexone were administered after a brief separation. Infants administered morphine (0.1 mg/kg IM) showed a significant reduction in clinging and girning, a vocalization emitted during close physical contact. Naltrexone (5 mg/kg IM) had opposite effects. When administered to mothers, again morphine decreased and naltrexone increased clinging. Morphine administered to mothers had a more transient behavioral effect which could not be accounted for by lower morphine blood levels. These results demonstrate that during reunion, the amount of intimate contact between a mother and her infant is regulated by the reciprocal activation of their opiate systems. This activation of opiate systems may reinforce the infant's need for attachment and the mother's role in care giving.

Animals↗
PubMed1995

Corticotropin-releasing factor (CRF) receptors in infant rhesus monkey brain and pituitary gland: biochemical characterization and autoradiographic localization.

A large body of data suggests that the corticotropin-releasing factor (CRF) system serves to coordinate the autonomic, endocrine, immune and behavioral aspects of the stress response. In rats, the distribution of CRF receptors in brain and pituitary has been well characterized, however, little information is available in primates. In this study, CRF receptors were characterized by radioligand binding and localized using autoradiography with [125I]-oCRF in the pituitary gland and in discrete brain regions of 2-week-old, 12-week-old and adult rhesus monkeys. Autoradiographic localization studies in slide-mounted tissue sections in the 2- and 12-week-old monkeys demonstrated high CRF receptor densities in both anterior and intermediate lobes of the pituitary as well as in discrete regions of the brain. The distribution of CRF receptors in the anterior pituitary demonstrated a 'cluster-like' appearance reminiscent of corticotrope distribution. In contrast, receptors in the intermediate lobe were more uniformly distributed. No significant differences were evident in the pattern of localization or the number of CRF receptors in the pituitaries of 2- compared to 12-week-old animals. However, marked differences were observed in the dentate gyrus of the hippocampus. Receptors in this region were absent in 1- to 2-week old animals but quite dense by 11-12 weeks of age. Conversely, in the lateral and medial geniculate nuclei, high levels of CRF receptors were identified early in life that virtually disappeared by 11-12 weeks of age. Thus, there is considerable correspondence in the development of the CRF system between the rat and rhesus monkey and this presents further evidence for the functional role of this peptide in brain development.

Animals↗
PubMed1994

Restraint stress increases corticotropin-releasing hormone mRNA content in the amygdala and paraventricular nucleus.

Corticotropin-releasing hormone (CRH) neurons located in the paraventricular nucleus (PVN) of the hypothalamus are implicated in regulating the endocrine response to stress. The amygdala is an established component of the neural circuitry mediating the stress response. To obtain information concerning the effects of stress on amygdala CRH neurons, a time-course study was conducted to examine, in rats, whether a 1-h restraint period increases CRH mRNA levels. The effects of restraint were also measured in the PVN. Using a sensitive RNase protection assay, we found that CRH mRNA levels in both the amygdala and paraventricular nucleus were significantly elevated 1 h after cessation of restraint. CRH mRNA levels in the paraventricular nucleus, but not the amygdala, remained elevated at the 3-h post-stress interval. 48 h after the termination of restraint, CRH mRNA levels in both brain structures returned to control levels. These data provide the first direct evidence that stress activates amygdala CRH neurons.

Amygdala↗
PubMed1993

Attenuation of stress-induced behavior by antagonism of corticotropin-releasing factor receptors in the central amygdala in the rat.

Research suggests that endogenous corticotropin-releasing factor (CRF) in the amygdala plays a role in the expression of stress-induced behavior. This study examined in rats whether antagonism of CRF receptors in the central amygdala (CA) region using alpha-helical CRF9-41, a CRF antagonist, was effective in attenuating the occurrence of stress-induced freezing. Bilateral infusions of 50, 100, or 200 ng of the CRF antagonist were made in the CA region using 33-gauge cannula immediately prior to testing. Freezing was measured in two test conditions. In one condition, the effects of the CRF antagonist on freezing was assessed immediately after exposure to electric foot shock. In the other condition, freezing was examined in shock-experienced rats that were re-exposed to the shock environment. Results suggested that 50 and 100 ng of the CRF antagonist were effective in reducing the duration of freezing in the immediate post-shock period. In addition, the 100 ng dose produced a significant reduction in freezing duration after rats were re-exposed to the shock environment. Collectively, data suggest that antagonizing the action of endogenous CRF in the CA region contributes to a general alleviation of stress-induced freezing.

Amygdala↗
PubMed1993

Lateralized response to diazepam predicts temperamental style in rhesus monkeys.

Based on previous findings in humans and rhesus monkeys suggesting that diazepam has asymmetrical effects on frontal lobe activity and other literature supporting a role for the benzodiazepine system in the mediation of individual differences in anxiety and fearfulness, the relation between asymmetrical changes in scalp-recorded regional brain activity in response to diazepam and the temperamental dimension of behavioral inhibition indexed by freezing time in 9 rhesus monkeys was examined. Animals showed greater relative left-sided frontal activation in response to diazepam compared with the preceding baseline. The magnitude of this shift was strongly correlated with an aggregate measure of freezing time (r = .82). The implications of these findings for understanding the role of regional differences in the benzodiazepine system in mediating individual differences in fearfulness are discussed.

Animals↗
PubMed1993

The neurobiology of fear.

Researchers are beginning to tease apart the neurochemical processes that give rise to different fears in monkeys. The results may lead to new ways to treat anxiety in humans.

Adrenal Glands↗
PubMed1992

Lateralized effects of diazepam on frontal brain electrical asymmetries in rhesus monkeys.

A growing body of literature has documented the differential role of the frontal regions of the two cerebral hemispheres in certain positive and negative affective processes. This corpus of evidence has led to the hypothesis of a possible differential effect of diazepam on asymmetry of frontal activation. To examine this question, nine infant rhesus monkeys were tested on two occasions during which brain electrical activity was recorded from left and right frontal and parietal scalp regions. During one session, recordings were obtained under a baseline restraint condition and then after an injection of diazepam (1 mg/kg). In the other session, following the same baseline restraint condition, a vehicle injection was given. In response to diazepam, the animals showed an asymmetrical decrease in power in the 4-8 Hz frequency band, which was most pronounced in the left frontal region. No change in electroencephalogram (EEG) activity was observed in response to vehicle. Asymmetry in parietal EEG activity was also unchanged by diazepam. Diazepam also produced overall reductions in power across different frequency bands in both frontal and parietal regions. Good test-retest stability of EEG measures of activation asymmetry was also found between the two testing sessions separated by three months. The possible proximal cause of the asymmetrical change in frontal brain electrical activity in response to diazepam, as well as the implications of these findings for understanding the mechanism of action of benzodiazepines are discussed.

Animals↗
PubMed1992

Antagonism of corticotropin-releasing factor receptors in the locus coeruleus attenuates shock-induced freezing in rats.

Intracerebroventricularly administered alpha-helical CRF9-41, a corticotropin-releasing factor (CRF) receptor antagonist, is known to reduce a variety of stress-induced behavioral responses. This study examined in rats whether antagonism of CRF receptors in the region of locus coeruleus (LC) plays a role in reducing freezing induced by electric foot shock. Freezing is a well-characterized defensive response to stress and has been demonstrated to index an animal's degree of fear. A CRF-receptor antagonist, alpha-helical CRF9-41, bilaterally infused into the LC significantly reduced the duration of freezing at a dose as low as 0.20 micrograms. Additional experiments confirmed that 0.20 micrograms of alpha-helical CRF9-41 significantly reduced the duration of freezing only when cannulae were within the LC or in regions bordering the nucleus. Antagonist-treated rats with cannulae that did not impinge on the LC exhibited freezing at levels not different from vehicle-treated animals. These results strongly implicate CRF receptors located in the LC region in influencing the display of stress-induced behavior.

Animals↗
PubMed1992

Effects of beta-carboline on fear-related behavioral and neurohormonal responses in infant rhesus monkeys.

We examined the effects of the inverse benzodiazepine agonist ethyl-beta-carboline-3-carboxylate (beta-CCE) on behavioral, hormonal, and neurochemical responses in infant rhesus monkeys exposed to fearful situations. Our paradigm elicits three distinct adaptive patterns of defensive behavior. From previous work, we hypothesized that behaviors induced by attachment bond disruption are predominantly mediated by opiate systems, whereas behaviors induced by the threat of attack are mediated by benzodiazepine systems. When beta-CCE (0, 125, 250, and 500 micrograms/kg) was administered immediately after maternal separation, the 500 micrograms/kg dose increased freezing and the 250 and 500 micrograms/kg doses reduced environmental exploration. Test conditions produced increased plasma ACTH and cortisol concentrations and increased cerebrospinal fluid (CSF) concentrations of MHPG and DOPAC; beta-CCE did not further affect these metabolites. A dose of 1000 micrograms/kg of beta-CCE increased CSF concentrations of DOPAC and MHPG in infants left with their mothers. During test conditions, it further increased CSF MHPG (but not DOPAC) concentrations, and reduced cooing while increasing freezing and barking and other hostile behaviors. Our results thus confirm that benzodiazepine systems mediate threat-related behaviors and suggest that coos, which were thought to predominantly reflect the degree of distress during separation, can be modulated by the infant's level of fear. beta-CCE also activated stress-related pituitary-adrenal hormonal systems and brain norepinephrine (NE) and dopamine (DA) systems. These effects occurred when animals remained undisturbed in their home cages with their mothers, suggesting that benzodiazepine receptors directly modulate brain NE and DA systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Prenatal stress alters brain catecholaminergic activity and potentiates stress-induced behavior in adult rats.

Previous studies demonstrated that throughout the preweaning period prenatally stressed rats have an overactive hypothalamic-pituitary-adrenal (HPA) system. This increased HPA activity was accompanied by an increase in defensive behavior. This study examined whether these alterations in HPA activity and defensive behavior continued into adulthood. Brain catecholamines in the cerebral cortex and locus coeruleus were also measured in prenatally stressed and control rats. Shock-induced levels of defensive freezing were significantly higher in prenatally stressed rats than in controls. However, plasma ACTH and corticosterone concentrations did not differ between groups either in the basal state or after exposure to foot shock. Concentrations of norepinephrine (NE) in the cerebral cortex and locus coeruleus region were significantly reduced in prenatally stressed rats. In addition, concentrations of NE metabolites were significantly elevated in prenatally stressed rats, suggesting an increased turnover of brain NE. Prenatally stressed rats also had, in the locus coeruleus region, significantly reduced dopamine (DA) levels but elevated concentration of DA metabolites. Results indicate that prenatal stress produces an increased behavioral responsiveness to stress that is evident in early life and continues into adulthood. The early hyperactivity of the HPA system in prenatally stressed rats, however, appears to normalize in adulthood. The increased turnover in brain catecholamines measure in the cerebral cortex and locus coeruleus region of prenatally stressed rats may be associated with the heightened expression of stress-induced behavior.

Adrenocorticotropic Hormone↗