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Role of noradrenergic projections to the bed nucleus of the stria terminalis in neuroendocrine and behavioral responses to fear-related stimuli in rats.

The bed nucleus of the stria terminalis (BNST) receives dense noradrenergic projections from the brainstem and has been claimed to play a role in expression of a variety of stress responses. Fear-related stimuli suppress vasopressin and facilitate oxytocin release from the neurohypophysis and induce behavioral suppression. Here we investigated in male rats whether conditioned fear stimuli increase noradrenergic activity in the BNST and whether depletion of epinephrine content in the BNST prevents neuroendocrine and behavioral responses to fear stimuli. Environmental stimuli previously paired with electric footshocks increased the ratio of 3-methoxy-4-hydroxyphenylglycol to norepinephrine contents in the BNST, suggesting that the stimuli activated noradrenergic projections to the BNST. 5-Amino-2, 4-dihydroxy-alpha-methylphenylethylamine, a neurotoxin relatively selective for noradrenergic fibers, when injected into the BNST 7 days before measurement, decreased the content of norepinephrine by 95% and that of dopamine or serotonin by about 50%. In the rats that received the neurotoxin, the suppressive vasopressin but not the augmentative oxytocin response to intermittent footshocks was abolished. In the experiments with conditioned fear stimuli, the neurotoxin given before training partially but significantly impaired the suppressive vasopressin and behavioral responses to testing stimuli. The neurotoxin given after training, however, did not prevent the vasopressin, oxytocin or behavioral responses. The results suggest that noradrenergic fibers in the BNST mediate the suppressive vasopressin but not the augmentative oxytocin response to nonassociatively applied fear stimuli and that they modulate, in a facilitative fashion, acquisition but not retention or recall of the emotional memory associated with the vasopressin and behavioral responses to conditioned fear stimuli.

Amygdala↗

Developmental change in infant cortisol and behavioral response to inoculation.

Infant cortisol and behavioral responses to receiving 1 versus 2 inoculations on 1 pediatric office visit were observed at 2 and 6 months of age. Cortisol level (pre- plus postinoculation level) decreased with age, whereas cortisol response (post- minus preinoculation level) did not vary with age when the data were aggregated over infants showing a pre- to postinoculation cortisol increase and those showing a decrease. Nonetheless, for those infants who showed a cortisol increase, cortisol level and response decreased with age. Infants quieted faster at the older age. There was a moderate relation between quieting behavior and cortisol response, at least for infants who showed a pre- to postinoculation cortisol increase. These findings indicate a developmental trend for a decline over age in adrenocortical reactivity to inoculation for infants showing a cortisol release following the perturbation. Results were comparable whether infants received 1 or 2 inoculations.

Diphtheria-Tetanus-Pertussis Vaccine↗

Peroneal afferent nerve discharges underlying the behavioral response to the formalin test.

BACKGROUND AND OBJECTIVES: Subcutaneous injection of formalin into the hindpaw of the rat results in a biphasic behavioral response consisting of flinching of the injected paw. It is postulated that the second-phase response is related to sensitization of spinal cord neurons rather than to resumption of peripheral nociceptor activity. METHODS: On removal from anesthesia with 3% halothane, 10 rats were given a subcutaneous injection of formalin (5%, 50 microL) into the dorsum of the hindpaw. Behavioral response to the formalin test were observed for the subsequent hour. In five sodium pentobarbital-anesthetized rats, peroneal afferent nerve activity was recorded for 1 hour following similar subcutaneous injection of formalin. RESULTS: During standard formalin testing in unanesthetized rats, flinching peaked between 1 and 2 minutes following injection (phase 1 response), ceased between 5 and 10 minutes, and recommenced after 15 minutes with a second peak at 45 minutes (phase 2). In sodium pentobarbital-anesthetized rats, peroneal afferent nerve activity increased transiently during the time course of the phase 1 behavioral response but showed no subsequent increase in activity during the ensuing 55 minutes. CONCLUSIONS: The results are consistent with the hypothesis that the initial behavioral response to formalin injection is mediated by high peripheral nerve activity, while the second phase is mediated by sensitization of dorsal horn neurons in conjunction with low persistent levels of afferent activity.

Animals↗

Differential responses of Aplysia siphon motor neurons and interneurons to tail and mantle stimuli: implications for behavioral response specificity.

1. Tail shock and mantle shock elicit different forms of siphon responses in Aplysia (flaring and backward bending vs. constriction and forward bending, respectively). Moreover, training with these two unconditioned stimuli (USs) in US-alone or classical conditioning paradigms differentially modifies the direction of the response to a siphon tap subsequently presented. As a first step toward addressing neural mechanisms underlying this response specificity, we systematically mapped the central siphon withdrawal circuit to determine which motor neurons and interneurons are differentially engaged by, and potentially modified by, tail and mantle USs. We utilized semi-intact preparations consisting of the intact mantle organs (including the gill and siphon), the tail, and the abdominal and circumesophageal ganglia. USs were delivered either cutaneously through silver wires implanted in the tail and mantle or via suction electrodes to the tail and branchial nerves. 2. We found that one class of central siphon motor neurons, the LFSB cells, was preferentially activated by tail USs, whereas other siphon motor neurons, the LBs cells and RDs cells, were preferentially activated by mantle USs. These motor neurons thus appear to be the final common path for the differential siphon movements to these USs. In addition, because activation of these cells can elicit neuromuscular facilitation and thereby enhance siphon movements, this differential activation may contribute to behavioral response specificity by imposing a specific response bias. 3. L29 interneurons, which both mediate and modulate the siphon withdrawal response, responded preferentially and exhibited synaptic facilitation selectively in response to tail shock USs. In contrast, L34 and the interneuron II network did not show differential activation. Facilitation at L29-LFSB connections following training with tail shock may contribute to tail-directed siphon responses to siphon tap and may thus be an additional mechanism contributing to behavioral response specificity. Possibly, facilitation at other L29 connections could also enhance its modulatory capabilities. 4. The generation of specific response topographies thus appears to involve the coordinate regulation of diverse neuronal elements and multiple mechanisms, which may contribute to different aspects of learning.

Animals↗

Stress-induced behavioral responses and multiple opioid systems in the brain.

Various stressor produce a wide range of behavioral responses such as analgesia, catalepsy and motor suppression, which are sensitive to opioid receptor antagonists. These behavioral responses in stress are accompanied by changes in the contents of opioid peptides, the mRNAs encoding their precursors and opioid receptor binding in the brain. In the present article, experimental data concerning stress-induced analgesia and motor suppression is reviewed and discussed in relation to a possible involvement of different opioid systems in the various observed behavioral responses in stress. Pharmacological studies with subtype-selective antagonists have demonstrated that not only mu- but also delta- and/or kappa-opioid receptors are involved in opioid-mediated stress-induced analgesia. There are two types of stress-induced analgesia referred to as opioid-mediated and non-opioid mediated forms. It has been proposed that the intensity and temporal pattern of stressor may be a critical factor determining the nature of stress-induced analgesia. Accumulated evidence demonstrate that these two forms of pain inhibitory systems interact each other according to a collateral inhibition model. Recent studies show that parallel activation of multiple opioid receptors mediates non-opioid froms of stress-induced analgesia. Dynorphins, by acting at kappa-opioid receptors, may play a pivotal role in the expression of stress-induced motor suppression, whereas enkephalins may act to attenuate this response.

Adaptation, Psychological↗

[Comparison of the effect of propofol and that of pentobarbital on behavioral responses to somatic and visceral stimuli in rats].

The behavioral responses to tail-flick and colorectal distension after intraperitoneal administration of either small or large dose of propofol as well as of pentobarbital were studied in rats. Immediately after baseline testing, animals were randomly divided into four groups; propofol groups of 50 mg.kg-1 (n = 4) or 100 mg.kg-1 (n = 4) and pentobarbital groups of 10 mg.kg-1 (n = 4) or 20 mg.kg-1 (n = 4). Both tests were repeated every 10 minutes for 1 hour in each group. There were no changes in the thresholds of colorectal distension and tail-flick latencies in those animals receiving small doses of propofol and pentobarbital. The thresholds for colorectal distension following administration of large doses of propofol and pentobarbital had greatly increased at 10 minutes and this increase persisted for about 30 minutes although it declined gradually. In contrast, the state of high sensitivity to tail-flick test was seen in the large dose groups of both drugs. It is concluded that there are no pharmacological differences between propofol and pentobarbital in behavioral responses to somatic and visceral stimuli in rats.

Animals↗

Organized behavioral responses to lateral hypothalamic electrical stimulation in infant rats.

Brief trains of electrical stimulation (500 msec) were administered to 3-, 6-, 10-, and 15-day-old rat pups through electrodes directed at the medical forebrain bundle (MFB) at the level of the lateral hypothalamus. Stimulation was given at three different frequencies: once per 30 sec, once per 20 sec, and once per 10 sec. Pups 10 days of age and younger became behaviorally activated by stimulation and reliably emitted a series of behavioral responses including mouthing, licking, pawing, gaping, probing, and stretch and lordosis responses. Behavior increased with increasing frequency of stimulation and became more organized with age. Sequences of organized behavior patterns are elicited by MFB stimulation which in their culmination take on the characteristics of motivational responses. Fifteen-day-old pups did not respond to these stimulation parameters. These findings indicate that the components of motivational systems are present and can be elicited at an early age. As development progresses, responses become more organized until stimulation parameters effective in rats 3 to 10 days of age become ineffective in activating behavior in day 15 pups.

Aging↗

IRI-514, a synthetic peptide analogue of thymopentin, reduces the behavioral response to social stress in rats.

Thymopentin, a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) corresponding to amino acids 32-36 of the thymic polypeptide thymopoietin, has been reported to block adrenocorticotrope responses to stress. The purpose of the present study was to explore potential antistress properties of a synthetic analogue of thymopentin, IRI-514 (Ac-Arg-Pro-Asp-Phe-NH2) using a behavioral response to a stressor. The behavioral response to social conflict stress (resident-intruder paradigm) was evaluated by the elevated plus-maze test of anxiety in adult Wistar rats. A single subcutaneous (SC) administration of IRI-514, 48 h before stress, dose-dependently reversed the anxiety-like behavior induced by the social stress. The effect of IRI-514 was present over an extended period (24-72 h) following SC administration and was maximally effective at a dose of 1 mg/kg. These results indicate that IRI-514 has a long-lasting modulatory effect on behavioral responses to a stressor, and suggest that thymopoietin-derived peptides may have a role in modulating both behavioral and neuroendocrine responses to stress.

Aggression↗

Behavioral response of altricial and precocial rodent fetuses to acute umbilical cord compression.

Norway rat fetuses (Rattus norvegicus) exhibit a stereotypic behavioral response when the umbilical cord is experimentally compressed with a vascular clamp. In this study, the development of the fetal behavioral response to cord compression was compared in altricial and precocial rodents, which differ markedly in neural and motor maturity at the time of birth. Both altricial and precocial species showed some form of behavioral response to umbilical cord compression. Fetuses of two altricial species, Norway rats and Mongolian gerbils (Meriones unguiculatus), expressed hyperactivity in response to cord compression throughout the last third of gestation. In contrast, precocial cotton rats (Sigmodon hispidus) and spiny mice (Acomys cahirinus) did not respond to cord compression until relatively late in gestation. Thus, altricial and precocial species do not express the cord compression response during comparable periods of neural development: precocial species are much more mature at the earliest expression of this behavior than altricial species. These findings are consistent with the interpretation that the cord compression response is a behavioral adaptation that can promote survival of the fetus in utero.

Animals↗

Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors.

Previous research has demonstrated that intrathecal i.t. morphine in a dose of 60.0 nmol into the spinal subarachnoid space of mice can evoke nociceptive behavioral responses consisting of a severe hindlimb scratching directed toward the flank followed by biting/licking of the hindpaw. The present study was undertaken to examine the involvement of spinal N-methyl-D-aspartate (NMDA) and opioid receptors on the behavioral responses evoked by high-dose i.t. morphine. Pretreatment with naloxone, an opioid receptor antagonist (1.0 and 4.0 mg/kg, s.c.), failed to reverse the morphine-evoked behavioral response, suggesting that the morphine effect is not mediated through the opioid receptors in the spinal cord. The morphine-induced behavior was dose-dependently inhibited by i.t. co-administration of the competitive NMDA receptor antagonists, D(-)-2-amino-5-phosphonovaleric acid (D-APV) (6.25-50.0 pmol) and 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (3.125-25.0 pmol). The characteristic behavior was also reduced by co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine maleate (MK-801) (74.1-250 pmol), an NMDA ion-channel blocker. Ifenprodil, a competitive antagonist of the polyamine recognition site of NMDA receptor ion channel complex, produced a dose-related inhibitory effect on the behavioral response to i.t. morphine with less potency than the competitive and non-competitive antagonists examined. High doses of (+)-HA-966, a glycine/NMDA antagonist, induced a dose-dependent inhibition of morphine-induced response. The effective dose of i.t. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, needed to reduce the morphine-induced response, was approximately 10-fold greater than that of D-APV. These results suggest that spinal NMDA receptors, but not non-NMDA receptors, may be largely involved in elicitation of the behavioral episode following i.t. injection of morphine in mice.

2-Amino-5-phosphonovalerate↗

Behavioral responses to aliphatic aldehydes can be predicted from known electrophysiological responses of mitral cells in the olfactory bulb.

For a better understanding of the encoding of odor quality in the olfactory system, it is critical to determine how electrophysiological responses to odorants are reflected in the behavioral responses to these odorants. In this article, we use a simple behavioral paradigm to show that the behavioral responses to similar odorants can be predicted from the electrophysiological responses of neurons in the olfactory bulb. Carbon chain length in aliphatic aldehydes has been used as a model for graded similarity among odorants. Recent electrophysiological experiments have shown that mitral cells in the rabbit olfactory bulb respond with similar response patterns to aliphatic aldehydes of similar chain length. On average, mitral cells responded with increased spiking activity to stimulation with two to three different aldehydes of neighboring chain length. We here show that the perception of these odorants can be predicted from the electrophysiological responses: rats that are conditioned to a given aldehyde generalize to aldehydes with one to two carbon differences in chain length from the conditioned aldehyde. When asked to discriminate between aldehydes of different chain lengths, rats learned to discriminate between any two odorants, but the rate of acquisition depended on the degree of similarity between the two odorants.

Aldehydes↗

The role of CRH in behavioral responses to stress.

Corticotropin-releasing hormone (CRH) and urocortin in the central nervous system affect behavior and can enhance behavioral responses to stressors. The action of CRH-related peptides is mediated through multiple receptors that differ markedly in their pharmacological profiles and anatomical distribution. Comparative pharmacology of CRH receptor agonists suggests that CRH, urocortin, sauvagine and urotensin consistently mimic, and CRH receptor antagonists consistently lessen, functional consequences of stressor exposure. Recently, important advances have been made in understanding the CRH system and its role in behavioral responses to stress by the development of specific CRH receptor antagonists, application of antisense oligonucleotides and development of transgenic mice lacking peptides and functional receptors. This review summarizes recent findings with respect to components of the CRH system and their role in stress-induced behavioral responses.

Animals↗

Effect of age on cold acclimation in rats: metabolic and behavioral responses.

To determine whether senescence affects the metabolic and behavioral responses of rats to chronic cold exposure, 8- and 22-mo-old male Fischer 344 rats were studied before and after 6 wk of cold (6-10 degrees C) exposure. Measurements of body weight, food consumption, oxygen consumption, body temperature, and ambient temperature selection in a thermocline (7-37 degrees C linear gradient) were made at regular intervals throughout the acclimation period. Before acclimation, age groups differed significantly only by weight. During acclimation, older rats had increased mortality and morbidity below 10 degrees C. After acclimation at 10 degrees C, younger and older rats both selected cooler ambient temperatures (7 and 5 degrees C cooler than preacclimation, respectively), and older rats had a significantly greater decrease in body temperature in the thermocline. Both age groups increased resting metabolic rate at 25 degrees C with cold acclimation (16.5 and 10% increase for younger and older rats, respectively). This study indicates distinct differences in metabolic and behavioral responses of younger and older rats to cold acclimation. Chronic cold exposure is detrimental to thermoregulatory function in older rats, since it is not as effective in stimulating sustained increases in metabolic rate in older rats as in young adults and it leads to a preference for cooler ambient temperatures, resulting in increased heat loss and reduced body temperature.

Acclimatization↗

Effects of copolymer concentration and chain length on the pH-responsive behavior of diblock copolymer micellar films.

The pH-responsive behavior of adsorbed diblock copolymer films of PDMA-PDEA (poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate)) on silica has been characterized using a quartz crystal microbalance with dissipation monitoring (QCM-D), an optical reflectometer (OR) and an atomic force microscope (AFM). The copolymer was adsorbed at pH 9 from various copolymer concentrations; QCM-D measurements indicate that the level of desorption when rinsed at pH 9 depends on the initial copolymer concentration. The adsorbed films produced at pH 9 generally have low charge densities; adjusting the solution pH to 4 results in a significant protonation of the constituent copolymers and a related interfacial structural change for the copolymer film. OR studies show no significant change during pH cycling, while QCM-D measurements indicate that the adsorbed mass and dissipation alter dramatically in response to the solution pH. The difference between the QCM-D adsorbed masses and dissipation values at pH 4 and 9 were found to be dependent on the initial copolymer concentration. This is due to differences in the initial conformations within the adsorbed copolymer layers at pH 9. The effect of the PDMA chain length on the pH-responsive behavior has also been studied; both the QCM-D adsorbed mass and dissipation of PDMA54-PDEA24 (shorter PDMA block) at pH 4 and 9 were observed to be greater than those of PDMA9X-PDEA2Y (longer PDMA block). This suggests that the normal extension of the adsorbed PDMA54-PDEA24 copolymer films is more significant than that of the PDMA9X-PDEA2Y films on silica.

Hydrogen-Ion Concentration↗

Seasonal variation in behavioral responses to m-CPP in patients with seasonal affective disorder and controls.

This paper reports the behavioral responses to m-chlorophenylpiperazine (m-CPP), a serotonin agonist, in patients with seasonal affective disorder (SAD) and controls during the summer. Results are compared with the responses of SAD patients and controls given m-CPP in the winter. Results of the winter study were reported earlier by our group. Baseline Hamilton depression ratings in SAD patients were significantly lower in the summer than in winter (p < 0.05). Additionally, in both SAD patients and controls, there were seasonal differences on the National Institute of Mental Health (NIMH) self-rating scale items: "depressed affect," "dysphoria," and "functional deficit" at baseline. The behavioral responses to m-CPP across seasons differentiated patients from normals only in the "activation/euphoria" item, on which a far greater response was seen in patients than in controls during the winter. This behavioral response may be a state marker for winter depression, as it was significantly reduced after light treatment of these patients in the winter, and in the summer. SAD patients responded differently from controls on "altered self-awareness" and "dysphoria" independently of seasons, and these responses may be considered as possible trait markers for this condition. These results provide further evidence of a possible deficiency in serotonergic transmission in seasonal affective disorder.

Adult↗

GABA(A)-receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol.

BACKGROUND: The gamma-aminobutyric acid type A receptors (GABARs) are involved in mediating some of the behavioral effects of beverage alcohol (ethanol). However, the unique pharmacological and behavioral responses conferred by each of the various receptor subunits are not well understood. METHODS: To address the role of the GABAR delta subunit in mediating ethanol responses, gene knockout mice that lack this subunit were tested for a variety of ethanol-induced behavioral responses. RESULTS: Our results indicate that, compared with controls, delta-deficient mice (delta-/-) have (1) reduced ethanol consumption, (2) attenuated withdrawal from chronic ethanol exposure, and (3) reduced anticonvulsant (seizure-protective) effects of ethanol. These mice demonstrate a normal anxiolytic response to ethanol and a normal hypothermic response to ethanol, and they develop both chronic and acute tolerance. CONCLUSIONS: These results further establish the link between GABARs and specific behavioral responses to ethanol and begin to reveal the role of the delta subunit in these responses.

Alcohol Drinking↗

Rapid behavioral response to corticosterone varies with photoperiod and dose.

The magnitude of the adrenocortical response to stress can be modulated by a variety of environmental and physiological factors, such as daylength and body condition. To determine the consequences of this modulation for the organism, one also needs to investigate behavioral sensitivity to glucocorticoids. We examined the behavioral response of Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) to elevated glucocorticoids. Using a behavioral assay in which a rapid and transient dose of corticosterone (CORT: the avian glucocorticoid) rapidly increases perch hopping, we first investigated the photoperiodic regulation of this behavioral response. Intermediate levels of CORT ( approximately 24 ng/ml), which increased activity in sparrows exposed to a long-day (breeding) photoperiod, had no behavioral effect in sparrows exposed to a short-day (winter) photoperiod. Hence, the neural mechanisms which regulate the behavioral response to CORT appear to be less sensitive under a winter photoperiod. Using the same behavioral assay, we also measured a dose-response curve for CORT's effects on activity in sparrows exposed to the long-day photoperiod. Intermediate levels (24 and 40 ng/ml) increased activity to threefold background levels, whereas high physiological levels (65 and 97 ng/ml) had no effect. Given that the behavioral response does not increase linearly with CORT, we can no longer assume that modulation of the adrenocortical response to stress will result in linear changes in behavior.

Animals↗

Glutathione-binding proteins identified by monoclonal antibodies which depress the behavioral response evoked by glutathione in Hydra.

Hydra shows at least 5 components of the behavioral response (R1-R5) which are evoked at different concentrations of S-methylglutathione (GSM). We have prepared several monoclonal antibodies (mAbs), each of which depressed specific responses and visualized specific structures. In this paper, we analyzed molecules participating in the signaling pathway of R5 response with use of three mAbs (J245, J5 and J5/1), all of which depressed the response. A behavioral analysis of the response in the presence of mixtures of these mAbs suggested that J245 and J5 both acted on a component of the receptor-effector system which was not affected by J5/1. Correspondingly, an immunoblotting analysis showed two 220 kDa proteins which reacted with both J245 and J5 but not with J5/1. ELISA analyses also showed that the J245 antigens formed only a portion of the J5 antigens. A labeled major peak was found in the 220 kDa protein fraction by gel permeation HPLC after immunoprecipitation of the J245 antigen photolabeled with [35S]-S-(p-azidophenacyl)-glutathione. Competition of the photolabeling by the ligands GSM and L-glutamate (a competitive inhibitor of the R5 response) indicated dissociation constants for their binding to the protein of 55 and 90 microM, respectively. These values were consistent with those expected from behavioral experiments. The 220 kDa proteins therefore appear to be candidates for the receptor molecules mediating R5.

Affinity Labels↗