Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabotropic glutamate (mGlu) receptors, which include mGlu1-8 receptors, are a heterogeneous family of G-protein coupled receptors (GPCRs) that function to modulate neuronal excitation and plasticity via pre-synaptic, post-synaptic and glial mechanisms. Agonists for group II mGlu receptors (mGlu2 and mGlu3), such as LY354740, have been shown to suppress enhanced glutamatergic excitations in brain synapses known to be involved in the expression of fear/anxiety in animals and humans. Systemic administration of LY354740 increases open-arm time in the elevated plus maze in mice under conditions of moderate to severe stress, blocks the expression but not development of fear-potentiated startle in rats, prevents lactate-induced panic-like responses in panic-prone rats, and attenuates certain physiological, behavioral, and neurochemical consequences of acute stress in rodents. In these preclinical models, LY354740 does not produce the side-effects (e.g. sedation) that are associated with other anxiolytic agents such as benzodiazepines. Early clinical results with LY354740 have demonstrated safety and efficacy in a human anxiety model (panic provocation induced by CO2 challenge). Collectively, these data indicate mGlu2/3 receptor agonists such as LY354740 represent a promising new approach for treatment of anxiety and stress-related disorders in humans.
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PMID:LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. 1312 12

A variety of data point to the possibility that neuroadaptations in glutamate transmission are produced by repeated exposure to cocaine that result in the expression of behaviors characteristic of addiction, such as craving and relapse. Using the reinstatement model of relapse in rats, glutamate release in the projection from the prefrontal cortex to the nucleus accumbens has been shown to underlie cocaine- and stress-primed reinstatement. In this report, four adaptations produced by withdrawal from repeated cocaine are described that may regulate the release of glutamate underlying reinstatement of drug-seeking resulted. (1) Neurons in the prefrontal cortex have increased levels of activator of G protein signaling 3 (AGS3) that causes reduced signaling through Gi coupled receptors, and normalization of AGS3 blocked cocaine-primed reinstatement. (2) The activity of the cystine-glutamate exchanger is reduced resulting in decreased extracellular glutamate in the nucleus accumbens, and normalization of exchanger activity prevented cocaine-primed reinstatement. (3) Metobotropic glutamate receptor function is diminished after repeated cocaine administration that results in reduced regulation of glutamate release. (4) Homer1 protein is reduced in the nucleus accumbens, and Homer2 knockout mice show enhanced responsiveness to cocaine. Taken together, there appears to be both pre- and postsynaptic changes in glutamate transmission that dysregulates the glutamatergic projection from the prefrontal cortex to the nucleus accumbens. These adaptations are hypothesized to facilitate glutamate release in response to a cocaine injection or acute stress and lead to the reinstatement of drug-seeking behavior.
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PMID:Glutamate transmission and addiction to cocaine. 1468 44

Superoxide has been shown to be an important intracellular mediator of actions of angiotensin II. Recently, we found that blockade of angiotensin II type-1 receptors in the rostral ventrolateral medulla (RVLM) abrogated the pressor effect of emotional stress in rabbits. In the present study, we examined the influence of superoxide dismutase mimetics, tempol and tiron, in RVLM on cardiovascular stress response in conscious rabbits. Air-jet stress evoked a sustained increase in blood pressure (+14+/-2 mm Hg), tachycardia (+52+/-7 bpm), and renal sympathoactivation (+58+/-8%). Bilateral microinjections of tempol or tiron (20 nmol) into RVLM did not alter resting cardiovascular parameters, but attenuated the pressor, sympathetic, and tachycardiac response to stress by 40% to 55%. By contrast, 3-carbamoylproxyl, which is structurally close to tempol but has a lower superoxide scavenging activity, did not alter the stress response. Neither tempol nor tiron altered the sympathoexcitatory response to glutamate microinjections into RVLM or to baroreceptor unloading. Microinjections of nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 10 nmol) into RVLM did not affect the stress response. Coinjections of tempol and L-NAME decreased the pressor response to stress by 35+/-3%. Tempol attenuated the pressor response to microinjection of angiotensin II into RVLM by 59+/-15%, whereas L-NAME did not alter this response. These results suggest that superoxide dismutase mimetics in RVLM attenuate, partially via a nitric oxide-independent mechanism, the pressor effect of emotional stress in rabbits. Together with our previous studies, these results also indicate that superoxide is a key mediator of excitatory actions of angiotensin II in RVLM during acute stress.
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PMID:Tempol attenuates excitatory actions of angiotensin II in the rostral ventrolateral medulla during emotional stress. 1515 79

Glutamatergic mechanisms are thought to be involved in stress-induced changes of brain function, especially in the hippocampus. We hypothesized that alterations caused by the hormonal changes associated with chronic and acute stress may affect glutamate uptake and release from hippocampal synaptosomes in Wistar rats. It was found that [3H]glutamate uptake and release by hippocampal nerve endings, when measured 24 h after 1 h of acute restraint, presented no significant difference. The exposure to repeated restraint stress for 40 days increased neuronal presynaptic [3H]glutamate uptake as well as basal and K+-stimulated glutamate release when measured 24 h after the last stress session. Chronic treatment also caused a significant decrease in [3H]glutamate binding to hippocampal membranes. We suggest that changes in the glutamatergic system are likely to take part in the mechanisms involved in nervous system plasticity following repeated stress exposure.
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PMID:Repeated restraint stress alters hippocampal glutamate uptake and release in the rat. 1545 65

1. The long-term level of arterial pressure is dependent on the relationship between arterial pressure and the urinary output of salt and water, which, in turn, is affected by a number of factors, including renal sympathetic nerve activity (RSNA). In the present brief review, we consider the mechanisms within the brain that can influence RSNA, focusing particularly on hypothalamic mechanisms. 2. The paraventricular nucleus (PVN) in the hypothalamus has major direct and indirect connections with the sympathetic outflow and there is now considerable evidence that tonic activation of the PVN sympathetic pathway contributes to the sustained increased level of RSNA that occurs in conditions such as heart failure and neurogenic hypertension. The tonic activity of PVN sympathetic neurons, in turn, depends upon the balance of excitatory and inhibitory inputs. A number of neurotransmitters and neuromodulators are involved in these tonic excitatory and inhibitory effects, including glutamate, GABA, angiotensin II and nitric oxide. 3. The dorsomedial hypothalamic nucleus (DMH) also exerts a powerful influence over sympathetic activity, including RSNA, via synapses with sympathetic nuclei in the medulla and, possibly, also other brainstem regions. The DMH sympathetic pathway is an important component of the phasic sympathoexcitatory responses associated with acute stress, but there is no evidence that it is an important component of the central pathways that produce long-term changes in arterial pressure. Nevertheless, it is possible that repeated episodic activation of this pathway could lead to vascular hypertrophy and, thus, sustained changes in vascular resistance and arterial pressure. 4. Recent studies have reactivated the old debate concerning the possible role of the baroreceptor reflex in the long-term regulation of sympathetic activity. Therefore, central resetting of the baroreceptor-sympathetic reflex may be an important component of the mechanisms causing sustained changes in RSNA. However, little is known about the cellular mechanisms that could cause such resetting.
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PMID:Long-term regulation of arterial blood pressure by hypothalamic nuclei: some critical questions. 1585 52

Animal models have shown progressive development and have undoubtedly proven their supportive value in OCD research. Thus, various animal models have confirmed the importance of the 5-HT [72-74] and dopamine systems [104,111] in the neurobiology and treatment of OCD. Given the neurochemical, emotional, and cognitive complexity of the disorder, how-ever, animal models are being used to investigate more and more complicated neurochemical and behavioral theories purported to underlie OCD. The lever-press model, for example, has implicated deficient response feed-back in a neural system that regulates operant behavior [74]. Studies on stereotypic movement disorder [89] have opened a new avenue of investigation into the neurobiology of stereotypy that may be applicable to more complex syndromes such as OCD. Models that have focused on specific neuropsychologic aspects of OCD such as reward [74], displacement behavior[63,101], perseveration and indecisiveness [73,102], and spontaneous stereotypy [90,94] are important in their attempt to unify the diverse behavioral manifestations of this disorder. It is clear that for a deeper, more holistic understanding of OCD, multiple animal models will be needed to allow investigation of the various aspects of the disorder and to provide convergent validation of the research findings. The heterogeneous nature of OCD, the various subtypes that exist within the disorder, and the range of obsessive-compulsive spectrum disorders suggest that particular questions regarding OCD may be addressed best by us-ing a particular ethologic model, whereas other questions might require a pharmacologic model or a combination of both for meaningful results[62,115]. Genetic models will be extremely useful for studying the genetics of pathologic behavior and for relating these findings to neuroanatomic and neurochemical changes in the model (eg, DICT-7 mice as a model for Tourette's syndrome and OCD). Neither ethologic nor pharmacologic models, however, can assess whether the "compulsive" behavior is a response to an "obsessive" anxiety or fear. Perhaps the symptoms seen in patients who have OCD, which may be exacerbated by everyday stress, are analogous to displacement behaviors in animals and also reflect some form of anxiety or stress [98]. In this regard, the bank vole model [116]has provided evidence that previously developed stereotypies increase markedly after acute stress and argues that healthy individuals "habituate" to everyday stress, whereas patients who have OCD do not. Interindividual variation in behavioral response and attempts to replicate studies in different laboratories often is the nemesis of the behavioral scientist. Small within- and between-subject variability is usually desirable, how-ever, because there are cases in which the study of the variability of the model could lead to a better understanding of the disorder. Variability can-not always be considered an error; it is possible that previously disregarded neuronal systems may have a place in the observed variation and, indeed, in the pathophysiology of OCD. In this regard, SRIs are not always effective for OCD [6,29,30] such that a lack of effect in a model may reflect an un-known neurobiological basis for compulsive behavior in a sub-group of SRI refractory patients. Similarly, separating the afflicted (ie, working with animals that show greater behavioral change in a model and/or after drug treatment) would have distinct benefits. To increase successful implementation of an ethologic animal model, especially when reinforcement models or signal attenuation models are used,the laboratory must be equipped with the essential behavioral testing apparatus as well as the operant chambers/rooms in which to conduct the train-ing and data collection. Quantification of certain stereotypy behaviors also requires experienced or trained observers. An illustration of the difficulty in measuring behavioral changes is that in the rewarded alternation model,a good response to behavioral treatment (alternation training) may lead to a floor effect [73] which, after successful drug treatment of the animal,produces no residual persistence (ie, measurable behavioral change) on which a drug treatment can be tested. Clearly, the choice of ethologic, pharmacologic, or genetic models should be considered carefully. A well-validated model may quell many of the limitations and considerations described previously. Noninvasive neuroimaging(eg, the use of small-animal single-photon emission CT) to explore the neuroanatomic basis of OCD offers an exciting future challenge, especially if combined with pharmacologic or ethologic models, and could confirm or ex-tend knowledge of the neuroanatomy of OCD. Although studies to investigate further the interactive role of 5-HT, dopamine, GABA, and glutamate are still needed, the role of neuroactive peptides such as cholecystokinin, corticotrophin-releasing factor, neuropeptide Y, tachykinins (ie, substance P),and natriuretic peptides in OCD should also be considered. Genetically engineered animal models will become increasingly valuable in combination with new technologies such as gene-chip microarrays, RNA interference, and advanced proteomics that will help further the understanding of OCD. Animal models of OCD are poised to play a vital role in extending the knowledge of the disorder now and in the future.
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PMID:Animal models of obsessive-compulsive disorder: rationale to understanding psychobiology and pharmacology. 1665 Jul 14

L-Theanine is an amino acid contained in green tea leaves which is known to block the binding of L-glutamic acid to glutamate receptors in the brain. Because the characteristics of L-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-Theanine at the start of an experimental procedure, one in which they took L-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that L-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of L-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation.
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PMID:L-Theanine reduces psychological and physiological stress responses. 1693 Aug 2

Behavioral stress facilitates long-term depression but impairs long-term potentiation in the hippocampus. Recent evidence in vitro demonstrates that the NR2B-containing N-methyl-D-aspartate subtype glutamate receptor antagonist Ro25-6981 prevents the behavioral stress-facilitated hippocampal long-term depression. It is, however, unknown whether Ro25-6981 influences hippocampal long-term depression and long-term potentiation induction in vivo under stressful condition. Here, we found that infusion of Ro25-6981 (2.3 microg in 6 microl, intracerebroventricular for 10 min) 30 min before low-frequency stimulation prevented the facilitation of hippocampal long-term depression by acute stress in anesthetized adult rats. Moreover, infusion of Ro25-6981 30 min before high-frequency stimulation reversed stress-impaired hippocampal long-term potentiation. These results suggest that the NR2B-containing N-methyl-D-aspartate subtype glutamate receptors are crucial for the effects of behavioral stress on hippocampal long-term depression and long-term potentiation in vivo.
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PMID:NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo. 1695 82

Glutamine is a non-essential amino acid that can be synthesized de novo from glutamate. This synthesis can be increased by intravenous infusion of carbon precursors (alpha-ketoglutarate or amino acids) in adults and in infants. The metabolism of glutamine is highly compartmentalized between the splanchnic tissues and the periphery, so that orally administered glutamine is completely metabolized in the splanchnic compartment. Data from studies in adults and children show that plasma levels of glutamine decline during acute stress and illness. Because of its importance in several physiological functions (the demonstrated benefits of supplemental glutamine in adult burns and trauma patients and the inhibitory effect on proteolysis in the skeletal muscle in vitro), it has been suggested that during 'acute stress' the demands of glutamine outweigh its de novo synthesis, resulting in a fall in plasma glutamine levels. As a consequence, glutamine has been considered a 'conditionally essential' amino acid. Because of its instability in solution, glutamine is not routinely added to the parenteral amino acid mixtures. A number of clinical trials of parenteral and enteral supplementation of glutamine have been performed. The outcome measures examined have varied between acute effects and long-term complex clinical events such as mortality and risk of infections. Although acute studies in LBW babies have shown some beneficial effects such as changes in protein metabolism and activation of immune system, these have not been translated into prolonged advantages such as reduction in mortality or in nosocomial infection. The reasons for these differences are discussed.
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PMID:Glutamine supplementation in the newborn infant. 1714 18

Acute stress impairs memory retrieval and facilitates the induction of long-term depression (LTD) in the hippocampal CA1 region of the adult rodent brain. However, whether such alterations in synaptic plasticity cause the behavioral effects of stress is not known. Here, we report that two selective inhibitors of the induction or expression of stress-enabled, N-methyl-D-aspartate receptor-dependent hippocampal LTD also block spatial memory retrieval impairments caused by acute stress. Additionally, we demonstrate that facilitating the induction of hippocampal LTD in vivo by blockade of glutamate transport mimics the behavioral effects of acute stress by impairing spatial memory retrieval. Thus, the present study demonstrates that hippocampal LTD is both necessary and sufficient to cause acute stress-induced impairment of spatial memory retrieval and provides a new perspective from which to consider the nature of cognitive deficits in disorders whose symptoms are aggravated by stress.
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PMID:Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment. 1759 37


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