Central noradrenergic neurones and stress

Stanford, S Clare

doi:10.1016/0163-7258(95)02010-1

Cited by 147 publications

(84 citation statements)

References 290 publications

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“…There is, however, a growing body of literature linking activation of noradrenergic transmission to the behavioral and physiological consequences of stress (Stanford, 1995;Bremner et al, 1996). Recent findings using rodent models of reinstated drug seeking suggest a potentially important role for the noradrenergic system in stress-induced relapse (Stewart, 2000;Shaham et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Blockade of α2-Adrenoceptors Induces Reinstatement of Cocaine-Seeking Behavior in Squirrel Monkeys

Lee

Tiefenbacher

Platt

et al. 2004

Neuropsychopharmacol

150

148

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Converging evidence suggests a role for noradrenergic mechanisms in stress-induced reinstatement of cocaine seeking in animals. Yohimbine, an a 2 -adrenoceptor antagonist, is known to be anxiogenic and induce stress-related responses in humans and animals. Here, we tested the ability of yohimbine to reinstate cocaine-seeking behavior and induce behavioral and physiological signs characteristic of stress in squirrel monkeys. Monkeys were trained to self-administer cocaine under a second-order schedule of i.v. drug injection. Drug seeking subsequently was extinguished by substituting saline for cocaine injections and omitting the cocaine-paired stimulus. The ability of yohimbine and the structurally distinct a 2 -adrenoceptor antagonist RS-79948 to reinstate cocaine-seeking behavior was assessed by administering priming injections immediately before test sessions in which the cocaine-paired stimulus was either present or absent. Priming injections of yohimbine (0.1-0.56 mg/kg, i.m.) or RS-79948 (0.01-0.1 mg/kg, i.m.) induced dose-related reinstatement of cocaineseeking behavior. The magnitude of yohimbine-induced reinstatement was similar regardless of the presence or absence of the cocainepaired stimulus. Yohimbine also significantly increased salivary cortisol levels, a physiological marker of stress, as well as scratching and selfgrooming, behavioral markers of stress in nonhuman primates. In drug interaction experiments, pretreatment with the a 2 -adrenoceptor agonist clonidine (0.1-0.3 mg/kg, i.m.) dose-dependently inhibited yohimbine-induced reinstatement of cocaine seeking. In contrast, pretreatment with the dopamine receptor antagonist flupenthixol failed to inhibit yohimbine-induced reinstatement of cocaine seeking. The results show that pharmacological blockade of a 2 -adrenoceptors can induce reinstatement of cocaine-seeking behavior and characteristic stress responses in squirrel monkeys, providing a potentially useful model of stress-induced relapse to drug seeking.

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Section: Introductionmentioning

confidence: 99%

Pharmacological Blockade of α2-Adrenoceptors Induces Reinstatement of Cocaine-Seeking Behavior in Squirrel Monkeys

Lee

Tiefenbacher

Platt

et al. 2004

Neuropsychopharmacol

150

148

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Section: Reboxetine Is a Selective Noradrenergic Reuptake Inhibitor Tmentioning

confidence: 99%

“…These neurons have been well characterized in awake and anesthetized animals and can be described as being sensitive to changes in the internal and external environment (Aston-Jones and Bloom 1981; Morilak et al 1987a,b). Thus, it is generally believed that dysregulation of this system may be an important factor in the onset of anxiety or depressive characteristics (Stanford 1995).The NE response to an acute stressor is characterized by a brief increase in extracellular NE with a return to basal levels shortly following termination of the stressor. In this study, an intermediate dose of reboxetine which elevates basal levels of NE, did not alter the response to the stressor compared with controls.…”

mentioning

confidence: 99%

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

Page

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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“…The noradrenergic system is postulated to play a primary role in an organism's response to stress (Stanford, 1995). Thus, it is well established that acute stress exposure can increase the discharge activity and NE release from noradrenergic LC neurons (Korf et al, 1973;Abercrombie and Jacobs, 1987;Abercrombie et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it is well established that acute stress exposure can increase the discharge activity and NE release from noradrenergic LC neurons (Korf et al, 1973;Abercrombie and Jacobs, 1987;Abercrombie et al, 1988). Furthermore, chronic exposure to stress can alter the response of LC neurons to subsequent stress exposure (for reviews see Stanford, 1993Stanford, , 1995Zigmond et al, 1995). For example, the activity of the rate-limiting enzyme in the synthesis of NE, tyrosine hydroxylase (TH), is increased in the LC following chronic exposure to cold, social stress, social isolation, or repeated exposure to restraint or foot shock (Zigmond et al, 1974;Stone et al, 1978;Angulo et al, 1991;Nisenbaum et al, 1991;Watanabe et al, 1995;Rusnak et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Chronic Exposure to Cold Stress Alters Electrophysiological Properties of Locus Coeruleus Neurons Recorded In Vitro

Jedema

Grace

2003

Neuropsychopharmacol

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Chronic stress exposure can alter central noradrenergic function. Previously, we reported that in chronically cold-exposed rats the release of norepinephrine and electrophysiological activation of locus coeruleus (LC) neurons is enhanced in response to multiple excitatory stimuli without alterations in basal activity. In the present studies, we used in vitro intracellular recording techniques to explore the effect of chronic cold exposure on the basal and evoked electrophysiological properties of LC neurons in horizontal slices of the rat brainstem. Consistent with our findings from in vivo experiments, chronic cold exposure did not affect basal firing rate. Furthermore, gross morphology of LC neurons and spike waveform characteristics were similar in slices from control and previously cold-exposed rats. However, excitability in response to intracellular current injection and input resistance were larger in slices from previously cold-exposed rats. In addition, the accommodation of spike firing in response to sustained current injection was smaller and the period of postactivation inhibition appeared to be less in LC neurons from cold-exposed rats. These data demonstrate that the stress-evoked sensitization of LC neurons observed in vivo is at least in part maintained in the slice preparation and suggest that alterations in electrophysiological properties of LC neurons contribute to the chronic stress-induced sensitization of central noradrenergic function observed in vivo. Furthermore, the present data suggest that an alteration in autoinhibitory control of LC activity is involved in the chronic stress-induced alterations. The enhanced functional capacity of LC neurons following cold exposure of rats may represent a unique model to study the mechanisms underlying the alterations in central noradrenergic function observed in humans afflicted with mood and anxiety disorders.

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Central noradrenergic neurones and stress

Cited by 147 publications

References 290 publications

Pharmacological Blockade of α2-Adrenoceptors Induces Reinstatement of Cocaine-Seeking Behavior in Squirrel Monkeys

Pharmacological Blockade of α2-Adrenoceptors Induces Reinstatement of Cocaine-Seeking Behavior in Squirrel Monkeys

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

Chronic Exposure to Cold Stress Alters Electrophysiological Properties of Locus Coeruleus Neurons Recorded In Vitro

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