Role of brain norepinephrine in the behavioral response to stress

Morilak, David A.; Barrera, Gabe; Echevarria, David J.; Garcia, Ana F.; Hernandez, Angelica; Ma, Shuaike; Petre, Corina O.

doi:10.1016/j.pnpbp.2005.08.007

Cited by 485 publications

(325 citation statements)

References 45 publications

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“…CRF administration has been shown to increase probe burying, while this behavior was blocked by CRF antagonists (Basso et al 1999;Diamant et al 1992;Korte et al 1994). Furthermore, shock-probe burying is accompanied by increases in NE transmission (Bondi et al 2007;Korte et al 1992) and attenuated by pretreatment with noradrenergic antagonists (Morilak et al 2005). Taken together, these data suggest that burying by rodents may be a model response for stress associated with the activation of NE pathways from the LC.…”

Section: Burying Behavior Is Mediated By Forebrain Nementioning

confidence: 84%

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

et al. 2008

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Rationale-Central administration of corticotropin-releasing factor (CRF) elicits a specific pattern of behavioral responses resembling a stress-like state, and is anxiogenic in rodent models of anxiety.Objectives-Specific behaviors evoked by the administration of CRF were measured. The roles of CRF receptor subtypes and that of serotonergic and noradrenergic systems in mediating these responses were studied.Methods-Burying, grooming and head shakes were quantified in rats following intracerebroventricular administration of CRF and urocortin II and after pretreatment with antagonists. The role of forebrain norepinephrine in the behavioral responses to CRF (0.3 μg) was examined following pretreatment with the neurotoxin DSP-4 and that of serotonin after depletion using systemic administration of para-chlorophenylalanine (p-CPA).Results-CRF at 0.3 and 3.0 μg caused robust increases in burying, grooming and head shakes, but urocortin II was ineffective. Pretreatment with either antalarmin or propranolol significantly attenuated the CRF-evoked behaviors. Destruction of forebrain NE pathways blocked spontaneous burying behavior elicited by CRF and conditioned burying directed towards an electrified shock probe. In contrast, depletion of 5-HT selectively attenuated CRF-evoked grooming.Conclusions-Overt behavioral responses produced by CRF, burying, grooming, and head shakes, appeared to be mediated through the CRF 1 receptor. Spontaneous burying behavior evoked by CRF or conditioned burying directed towards a shock probe were disrupted by lesion of the dorsal noradrenergic bundle and may represent anxiety-like behavior caused by CRF activation of the LC. In contrast, CRF-evoked increases in grooming were dependent on serotonin.

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Section: Burying Behavior Is Mediated By Forebrain Nementioning

confidence: 84%

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

et al. 2008

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“…The effects of escitalopram, a serotonin reuptake blocker, were more complex, in that the detrimental effect of chronic unpredictable stress was attenuated, but escitalopram alone also induced a baseline deficit in ED set shifitng. The noradrenergic system is highly responsive to stress (e.g., see review in Morilak et al 2005). However, depending on the nature of the stress, e.g., psychogenic or metabolic, different neural pathways and neurotransmitter systems may be invoked (e.g., see Herman et al 2005;Sawchenko et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

et al. 2008

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Rationale-Chronic stress perturbs modulatory brain neurotransmitter systems, including serotonin (5-HT), and is a risk factor for psychiatric disorders such as depression. Deficits in cognitive flexibility, reflecting prefrontal cortical dysfunction, are prominent in such disorders. Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT.Objectives-Assess the effects of chronic intermittent cold (CIC) stress, a potent metabolic stressor, on performance of rats in an attentional set shifting test (AST). Assess a possible role for serotonin in CIC-induced deficits, and test the effects of acute serotonin reuptake blockade. Methods-MaleSprague-Dawley rats were exposed to CIC stress (14 days × 6 hr/day at 4 °C) before testing on the AST. In subsequent experiments, brain 5-HT was depleted in naïve rats with para-chlorophenylalanine, or 5-HT release was increased acutely in CIC-stressed rats with citalopram (5 mg/kg, s.c.) given 30 min prior to the first reversal task. Microdialysis was used to assess CICinduced changes in 5-HT release in OFC during testing.Results-CIC-stressed rats exhibited a selective impairment on the first reversal task in the AST. 5-HT depletion induced a similarly selective deficit in reversal learning. The CIC-induced impairment in reversal learning was attenuated by acute 5-HT reuptake blockade. 5-HT release was reduced in OFC of CIC-stressed rats during behavioral testing.Conclusions-The CIC stress-induced impairment of cognitive flexibility may involve dysregulation of 5-HT modulatory function in OFC. Such deficits may thus model relevant symptoms of neuropsychiatric disorders that respond positively to SSRI treatment.

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“…Moreover, in addition to the older norepinephrine (NE)-specific tricyclic drug, desipramine (DMI), a newer generation of selective NE reuptake inhibitors have emerged recently as effective treatments for affective disorders (reviewed in Frazer, 2000Frazer, , 2001Morilak and Frazer, 2004). Activation of the brain NA system exerts a widespread modulatory influence that facilitates a variety of autonomic, neuroendocrine, cognitive, and behavioral processes, which in turn may contribute to behavioral state changes such as increased arousal, or to adaptive responses to acute stress (Aston-Jones et al, 1991, 2000Morilak et al, 2005). In this way, enhancing NA function may be beneficial in the treatment of depression and anxiety (see Morilak and Frazer, 2004).…”

Section: Introductionmentioning

confidence: 99%

Chronic Treatment with Desipramine Improves Cognitive Performance of Rats in an Attentional Set-Shifting Test

Lapiz

Bondi

Morilak

2006

Neuropsychopharmacol

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Alterations in central monoaminergic neurotransmission are important in the actions of many antidepressants. This study tested the hypothesis that tonic elevation of noradrenergic (NA) neurotransmission in medial prefrontal cortex (mPFC) by chronic treatment with the selective norepinephrine (NE) reuptake blocker desipramine (DMI) may contribute to the beneficial cognitive effects of this antidepressant drug (AD). Male Sprague-Dawley rats were treated with DMI acutely (15 mg/kg, i.p.) or chronically for 21 days (7.5 mg/ kg/day via osmotic minipump) before assessing performance on an attentional set-shifting test. The extradimensional set-shifting component of this test reflects a process of cognitive flexibility that is dependent upon mPFC, and that we have shown previously to be facilitated by NA activity in mPFC. Microdialysis was performed to measure NE release in mPFC concurrently with behavioral testing. Acute DMI treatment produced an increase in extracellular NE levels in mPFC, and a modest improvement in overall performance across all task stages of the attentional set-shifting test, but failed to produce a significant improvement in any of the individual specific tasks comprising the test sequence. Chronic DMI treatment tonically elevated basal extracellular NE levels in mPFC, associated with a significant improvement in performance specifically on the extradimensional set-shifting component of the test. There was also a significant reduction in set loss errors in rats treated chronically with DMI. Hence, tonic elevation of NA transmission in mPFC by chronic DMI treatment was associated with a time-dependent facilitation of cognitive flexibility that may contribute to the mechanism whereby chronic treatment with ADs, specifically NE reuptake blockers, may exert a beneficial therapeutic effect on cognition in depressed patients.

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Role of brain norepinephrine in the behavioral response to stress

Cited by 485 publications

References 45 publications

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin in rats

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

Chronic Treatment with Desipramine Improves Cognitive Performance of Rats in an Attentional Set-Shifting Test

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