Central Norepinephrine Metabolism During Alcohol Intoxication in Addicts and Healthy Volunteers

Borg, Stefan; Kvande, Hans; Sedvall, Göran

doi:10.1126/science.7268421

Cited by 108 publications

(32 citation statements)

References 11 publications

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“…We thus wanted to examine if stressful manipulations, which would increase adrenergic tone in vivo, could alter the expression of α 1 -AR LTD ex vivo. Withdrawal from alcohol intoxication has been shown to increase anxiety (40), and patients experiencing withdrawal have elevated levels of NE and its metabolites (36,41). Furthermore, CIE can increase anxiety-like behavior in animal models (44).…”

Section: Discussionmentioning

confidence: 99%

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Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

McElligott

Klug

Nobis

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Long-term depression (LTD) is an important synaptic mechanism for limiting excitatory influence over circuits subserving cognitive and emotional behavior. A major means of LTD induction is through the recruitment of signaling via G q -linked receptors activated by norepinephrine (NE), acetylcholine, and glutamate. Receptors from these transmitter families have been proposed to converge on a common postsynaptic LTD maintenance mechanism, such that hetero-and homosynaptic induction produce similar alterations in glutamate synapse efficacy. We report that in the dorsolateral and ventrolateral bed nucleus of the stria terminalis (BNST), recruitment of G q -linked receptors by glutamate or NE initiates mechanistically distinct forms of postsynaptically maintained LTD and these LTDs are differentially regulated by stress exposure. In particular, we show that although both mGluR5-and α 1 -adrenergic receptor (AR)-dependent LTDs involve postsynaptic endocytosis, the α 1 -AR-initiated LTD exclusively involves modulation of signaling through calcium-permeable AMPA receptors. Further, α 1 -AR-but not mGluR5-dependent LTD is disrupted by restraint stress. α 1 -AR LTD is also impaired in mice chronically exposed to ethanol. These data thus suggest that in the BNST, NE-and glutamate-activated G q -linked signaling pathways differentially tune glutamate synapse efficacy in response to stress.addiction | norepinephrine | metabotropic glutamate receptor | calcium-permeable AMPA receptor | ethanol A lterations in key amygdalar and reward circuitries have been proposed as potential mechanisms underlying interrelated anxiety disorders and addiction. The bed nucleus of the stria terminalis (BNST) is a nucleus within a series of structures known as the "extended amygdala," which receives a mix of glutamatergic inputs from cognitive and systemic brain centers and projects to key nuclei in both the reward and stress circuitries (1, 2). Consistent with this anatomy, a large literature indicates key roles of this region in anxiety-related behaviors, addiction, and other affective disorders (3).The BNST receives intense noradrenergic innervation through the ventral noradrenergic bundle (VNAB) (4). Disruption of the VNAB or noradrenergic signaling in the BNST alters responses to stressors, preference for opiates, and stress-induced reinstatement to drug seeking (5, 6). α 1 -Adrenergic receptors (ARs) are G qlinked G-protein-coupled receptors (GPCRs) that participate in shaping responses to stressors. Signaling through BNST α 1 -ARs within the BNST potently regulates the hypothalamic-pituitaryadrenal (HPA) stress axis and anxiety responses after stressors (7). The α 1 -AR antagonist prazosin has been shown to attenuate ethanol self-administration (SA) in ethanol-dependent rats (8) and reduces opiate SA (9). Furthermore, data from clinical trials have demonstrated that prazosin alleviates symptoms of posttraumatic stress disorder (PTSD) (10) and reduces alcohol drinking behavior in alcoholics (11).Like α 1 -ARs, group I metabotropic glutamat...

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Section: Discussionmentioning

confidence: 99%

“…Stress disorders and alcoholism are highly comorbid (35). Data from human studies suggest that NE is increased in the central nervous system (CNS) of alcoholics (36), where it may play a role in the pathogenesis of alcoholism (35). Additionally, the adrenergic system remains an attractive target for intervention in alcoholism (11).…”

mentioning

confidence: 99%

Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

McElligott

Klug

Nobis

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Their higher BELs indicated that the higher habitual alcohol intake has not led to faster metabolism of etha nol as might be expected [56,57] but rather confirms observations from other studies that either no [ 18,58] or even positive relationships may be observed between amount of voluntary intake of alcohol and BEL upon acute exposure in animals [59] or men [60] possibly due to faster absorption to peak levels [61] supporting a genetically determined rate of metabolism [62,63] which has been shown to be a stable individual charac teristic [64], Lower fluid-induced NE release in HC may again be taken as evidence for lower noradrenergic responsiveness to a physical stimulus as observed with venipuncture, and a negative correlation between BEL and NE increase in the HC ethanol group (r = -0.54, p < 0.05) may, in addition, indicate tolerance of the norad renergic system to ethanol (since acute intake would induce dose-dependent increases of central nervous NE turnover in nontolerant subjects, as demonstrated by CSF analyses in healthy volunteers [65,66], But also lower respective baseline NE brain metabolism (turn over in CSF or DBH in plasma) observed in subjects with higher habitual alcohol intake [65,67] or with higher sensation seeking scores [30] would support the observation of a reduced general noradrenergic turnover in high alcohol consumers.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Drinking Habit on Catecholamine and Behavioral Responses to Stress and Ethanol

Netter

Vogel

1990

Neuropsychobiology

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The effects of alcohol tolerance on stress sensitivity to venipuncture and mental arithmetics, on acute ethanol effects, and on ethanol-induced modifications of stress responses were tested in 44 healthy male volunteers selected according to a questionnaire as 22 high (HC) and low (LC) habitual consumers of alcohol each. Plasma epinephrine (E) and norepinephrine (NE), mood check lists, and performance scores were obtained at two mental arithmetic stressors, one applied before and one after their intake of 0.8 g/kg of ethanol or a respective placebo drink. HC were less responsive with both E and NE to venipuncture and to mental stress regarding emotional and NE changes though showing higher E increases. Ethanol blood levels in HC were higher but ethanol-induced NE changes lower than in LC. The E, NE, and emotional stress responses were less reduced and performance less impaired by ethanol in HC than in LC. This was taken as evidence that neither stress nor ethanol sensitivity is increased in alcohol-preferring subjects but that tolerance by chronic intake of moderate doses of alcohol will result in a reduced efficacy of ethanol both on the psychological and biochemical levels, although effects on these two levels have not been found to be intraindividually related.

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“…При нормальном состоянии альфа 2 рецепторы ингибируют работу пресинап тического норадреналового нейрона. При абстинентном синд роме альфа 2 рецепторы становятся менее чувствительными, что приводит к неспособности норадренергичекой системы регулировать свою работу [62,63]. Многочисленные исследо вания подтверждают эффективность применения перораль ного и трансдермального клонидина (старейшего альфа 2 агониста), в снижении симптомов синдрома отмены, относя щихся к симпатической активации (особенно гипертензии и тахикардии) [64].…”

Section: распознание и лечение алкогольного абстинентного синдрома в unclassified

Psychomotor Agitation in Critically Ill Patients and the Role of Sedation

ФедарауМ.¹,

Комполо²,

Papadokos³

2012

rmt

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О Б Щ А Я Р Е А Н И М А Т О Л О Г И Я , 2 0 1 2 , V I I I ; 6 62 www.niiorramn.ru Существующая проблема психомоторных расст ройств, таких как возбуждение, тревога и делирий, многие годы привлекает внимание врачей и сестер отделений реани матологии, а также руководства больниц. Эти состояния мо гут напрямую влиять на оказание медицинской помощи больным, увеличивать их метаболические потребности и в конечном счете увеличивать заболеваемость и летальность. Данные состояния также связаны с увеличением продолжи тельности и стоимости нахождения больных в отделениях реаниматологии. В настоящее время дыхательная недоста точность является наиболее частой причиной поступления больных в отделение реаниматологии и сопровождается вы сокой летальностью. Однако только 16% больных, которым проводится искусственная вентиляция легких, умирают не посредственно от дыхательной недостаточности [1][2][3]. Сре ди внелегочных факторов, влияющих на летальность боль ных в критическом состоянии, возбуждение и делирий оста ются недооцененными и плохо изученными. В связи с этим необходима разработка и применение рекомендаций с сис темным и организационным подходом, направленных на профилактику и лечение данных нарушений.В течение последнего десятилетия были приняты реко мендации и протоколы, посвященные проведению седации в отделении реаниматологии и направленные на поддержание оптимального уровня комфорта и безопасности больных в критическом состоянии [4,5]. Седация и обезболивание рас сматриваются как жизненно важные мероприятия в течение всего периода госпитализации. Это приводит к увеличению усилий медицинского персонала, направленных на седацию и анальгезию у этой категории больных. В последнее время кли ницисты столкнулись со значительной нехваткой седативных препаратов, что повлияло на локальные протоколы отделений реаниматологии по всему миру. Наше растущее понимание важности изменений ментального статуса у больных в крити ческом состоянии и их влиянии на исход в свою очередь по влияло на тактику седации в отделениях реаниматологии. Это привело к изменению оценки и методов лечения больных.Critically ill patients often receive analgesia and sedation to keep them comfortable and to prevent agitation and delirium, which are serious, common and yet frequently underdiagnosed forms of brain dysfunction in intensive care environment with unclear but often unfavorable contribution to patient outcomes. Apart from delirium assessment and screening the most important aspect of ICU management is understanding the drugs given to patients and their specific advantages and disadvantages. It is crucial for clinicians and units to develop guidelines and protocols for the administration of sedatives depending on the type of patient population. Newer drugs, such as dexmedetomidine and remifentanyl, should be intro duced and extensively studied. The immunomodulating effects of sedation also must be explored, as these properties may greatly affect outcome. With an increased understanding of sedative drugs will come an improved ability to use multiple dru...

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Central Norepinephrine Metabolism During Alcohol Intoxication in Addicts and Healthy Volunteers

Cited by 108 publications

References 11 publications

Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

The Effect of Drinking Habit on Catecholamine and Behavioral Responses to Stress and Ethanol

Psychomotor Agitation in Critically Ill Patients and the Role of Sedation

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Central Norepinephrine Metabolism During Alcohol Intoxication in Addicts and Healthy Volunteers

Cited by 108 publications

References 11 publications

Distinct forms of G q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

Distinct forms of G q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

The Effect of Drinking Habit on Catecholamine and Behavioral Responses to Stress and Ethanol

Psychomotor Agitation in Critically Ill Patients and the Role of Sedation

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Product

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Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress

Distinct forms of G _q -receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress