II. New evidence for a locus coeruleus-norepinephrine connection with anxiety

Redmond, D. Eugene; Huang, Yung H.

doi:10.1016/0024-3205(79)90087-0

Cited by 650 publications

(123 citation statements)

References 77 publications

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“…The involvement of NE in stress-induced behavior in the MCC is consistent with the reported involvement of NE in emotional and behavioral responding associated with anxiety in humans (Hoehn-Saric et al, 1981;Charney et al, 1984) and nonhuman primates (Redmond and Huang, 1979). For example, monkeys in which the locus coeruleus was electrically stimulated or that received the oc,-antagonists piperoxan or yohimbine displayed fear-associated behaviors (Redmond and Huang, 1979). In rats, clonidine decreased the potentiated startle response (Davis et al, 1977) and increased punished responding in the Geller-Seifter conflict test (Kruse et al,198 1).…”

Section: Discussionsupporting

confidence: 86%

“…The fact that DSP-4 primarily affects fibers ofthe DNB (Jonsson et al,198 1) suggests that CRF affects exploratory behavior by acting within the telencephalon, although other sites cannot be excluded. The involvement of NE in stress-induced behavior in the MCC is consistent with the reported involvement of NE in emotional and behavioral responding associated with anxiety in humans (Hoehn-Saric et al, 1981;Charney et al, 1984) and nonhuman primates (Redmond and Huang, 1979). For example, monkeys in which the locus coeruleus was electrically stimulated or that received the oc,-antagonists piperoxan or yohimbine displayed fear-associated behaviors (Redmond and Huang, 1979).…”

Section: Discussionsupporting

confidence: 79%

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Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF

1989

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Exploratory behavior, measured by the time an animal spends investigating objects in a novel environment, has been shown to be sensitive to prior exposure of the animal to stressors. or the number of rears. These results implicate noradrenergic systems in the stress-related changes in this behavior, consistent with our parallel measures of the production of NE catabolites. Thus, both CRF and noradrenergic systems appear to be involved in the effect of restraint on exploratory behavior in this task. Neither DSP-4 nor prazosin had any effect on the CRFinduced decrease in exploratory behavior. However, the CRF antagonist a-helical CRF,,, (20 fig, i.c.v.) reversed the decrease in exploratory behavior induced by phenylephrine. The most likely explanation is that the 2 systems act in tandem such that noradrenergic systems regulate the release of brain CRF via an a,-adrenoreceptor.This arrangement parallels that involved in the release of hypothalamic CRF to activate the pituitary-adrenal axis. The implications of these results for research on stress-related behaviors and for the etiology of depression are discussed.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 79%

Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF

1989

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“…Prolonged or repeated stress has been implicated in the precipitation of affective disorders (Abercrombie and Zigmond 1995;Charney et al 1993;Redmond and Huang 1979). It is generally thought that response of the noradrenergic system is important to mediate stress responses but perhaps the ability to effectively terminate that response becomes compromised following chronic stress.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acute and Chronic Reboxetine Treatment on Stress-induced Monoamine Efflux in the Rat Frontal Cortex

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2002

Neuropsychopharmacology

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Reboxetine is a selective noradrenergic reuptake inhibitor that displays an antidepressant profile in both animal tests and in clinical trials. The present study examined the ability of reboxetine to alter stress-induced increases in norepinephrine, serotonin and dopamine efflux in the frontal cortex in awake behaving rats. Acute systemic administration of reboxetine (0.3-20.0 Despite widespread efforts to understand the mechanisms of action of antidepressant drugs, the requisite changes in neural function that underlie their therapeutic effects remain unclear. Much evidence exists that points to dysfunction of the norepinephrine (NE), serotonin (5-HT) and dopamine (DA) neurotransmitter systems in depression. For example, it is known that drugs that alter monoamine neurotransmission provide some relief of depressive symptomatology. However, the pathophysiology associated with this disorder is not clear (Heninger and Charney 1987;Ressler and Nemeroff 2000;Schildkraut 1965). Furthermore, the acute pharmacological actions of many compounds at biogenic amine transporter sites do not account for the delay in onset of therapeutic effects. A therapeutic response is typically only observed following chronic treatment regardless of the particular class of drug or mode of treatment (Blier and DeMontigny 1994). A number of studies suggest that functional changes in receptor sensitivity following antidepressant treatment are required and may account, at least in part, for the therapeutic lag observed. For example, the downregulation of a variety of receptor subtypes, including ␤ -and (Blier and DeMontigny 1994).In the past, traditional antidepressant compounds such as the tricyclics were known to increase synaptic availability of NE, and thus an emphasis on the role of NE in both the pathogenesis of affective disorders and in the mechanism of action of antidepressant medications has driven much of the work in this field (Frazer 2000;Schildkraut 1965). However, most tricyclic compounds are associated with a large adverse side effect profile that contributes to low compliance among patients (Frazer 2000). The advent of the selective serotonin reuptake inhibitors (SSRIs), which have a lower side-effect profile, shifted the emphasis toward a potential crucial role of serotonergic dysfunction in affective disorders. Although a reduction in side effects associated with SSRIs has contributed to their popularity, many patients remain treatment resistant. A continuing effort to identify more efficacious antidepressant compounds has led to the emergence of the selective NE reuptake inhibitors (see Brunello and Racagni 1998). Reboxetine selectively inhibits the reuptake of synaptic NE without any marked affinity for other receptors or transporters (Wong et al. 2000). Additionally, reboxetine has been shown to be both clinically effective and well tolerated with a lower side-effect profile than tricyclics (Burrows et al. 1998).The present studies sought to characterize the impact of reboxetine treatment on monoaminergic neurotransmis...

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“…Several sources of physiological and pharmacological evidence support the link between SDB expression and anxiety (Crawley et al 1985;Maestripieri et al 1992;Ninan et al 1982;Redmond and Huang 1979;Schino et al 1991Schino et al , 1996. The laboratory-based studies prompted nonexperimental, observational studies on emotional states of nonhuman primates over the last 2 decades.…”

Section: Introductionmentioning

confidence: 99%

Correlates of Self-directed Behaviors in Captive Cercopithecus aethiops

2008

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Researchers have widely used self-directed behaviors (SDB) as a behavioral indicator of anxiety in nonhuman primates. We examined if SDB rates in captive vervets (Cercopithecus aethiops) were associated with 1) proximity to conspecifics in general, 2) relative dominance rank of proximity partners, and 3) postconflict situations. Subjects were members of a captive group of vervets at the Lisbon Zoo, Portugal. The group comprised 3 males and 7 females, which were focal sampled for 10.5 h each. Vervets did not engage in more SBD while in proximity of conspecifics than while alone, and individual SDB rates were not generally influenced by dominance ranks of neighbors. Yet, victims of conflicts significantly increased their SDB rates after agonistic episodes, which is consistent with the view that SDB rates are an index of anxiety in Cercopithecus aethiops.

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II. New evidence for a locus coeruleus-norepinephrine connection with anxiety

Cited by 650 publications

References 77 publications

Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF

Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF

Effects of Acute and Chronic Reboxetine Treatment on Stress-induced Monoamine Efflux in the Rat Frontal Cortex

Correlates of Self-directed Behaviors in Captive Cercopithecus aethiops

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