Evidence for Functional Release of Endogenous Opioids in the Locus Ceruleus during Stress Termination

Curtis, Andre L.; Bello, Nicholas T.; Valentino, Rita J.

doi:10.1523/jneurosci.21-13-j0001.2001

Cited by 86 publications

(98 citation statements)

References 30 publications

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“…Recent physiological evidence suggests that this is maintained in part through reciprocal regulation of the LC-NE system by CRF and opioids (Curtis et al, 2001). Convergence of CRF-and enkephalin-immunoreactive axon terminals onto LC dendrites (Tjoumakaris et al, 2003), taken with the present evidence for coexistence of CRF-R and -OR in dendrites in the LC, provides anatomical support for this.…”

Section: Discussionmentioning

confidence: 99%

“…During this challenge, CRF afferents are engaged to increase LC neuronal activity, and this is temporally correlated with, and necessary for, cortical EEG activation (Valentino et al, 1991;Page et al, 1993). After stress termination, opioid release inhibits LC neurons, restoring basal activity (Curtis et al, 2001) and presumably protecting against adverse consequences of continued activation (e.g., hyperarousal).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress

Bockstaele²,

Reyes³

et al. 2004

J. Neurosci.

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Chronic opiate use produces persistent changes in brain neurons that are expressed as adverse effects, including physical dependence and compulsive drug-seeking behavior. Dysregulation of the hypothalamic-pituitary-adrenal response to stress also occurs with chronic opiate administration and has been implicated as a contributing factor to continued substance abuse. This study provides the first evidence for dysregulation of the central noradrenergic response to stress by chronic opiates. Chronic morphine selectively sensitized locus ceruleus (LC)-norepinephrine (NE) neurons to corticotropin-releasing factor (CRF), an integral mediator of the stress response. CRF doses that were inactive in vehicle-treated rats produced a near-maximal activation of LC neurons of rats chronically administered morphine. LC sensitization to CRF was not solely a pharmacological phenomenon but was expressed as hyperresponsivity to physiological stress. Finally, opiate-induced LC sensitization translated to a change in the behavioral repertoire in response to environmental stress (swim stress) such that NE-mediated hyperactive behaviors predominated. The opiate-induced sensitization of the central NE response to stress predicts that chronic opiate administration increases vulnerability to certain stress-related symptoms (e.g., hyperarousal, attentional dysfunction), and this may contribute to the maintenance of opiate-seeking behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress

Bockstaele²,

Reyes³

et al. 2004

J. Neurosci.

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“…The antidepressant effect of SD is, however, not believed to be related to the associated anxiolytic-like process (47). In addition, abovementioned effects may partly be attributed to the release of endogenous peptides in response to stress following SD (48).…”

Section: Discussionmentioning

confidence: 99%

Aversive Memory, Anxiety-Related Behaviors, and Serum Neurochemical Levels in a Rat Model of Labored Sleep Loss

et al. 2014

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Background: Sleep deprivation (SD) is emerging as a hot topic due to its health concerns. There are compelling reasons for a tremendous interest in neuroscience of sleep in recent years. Objectives: We aimed to evaluate how total sleep deprivation (TSD) and chronic partial sleep restriction (CPSR) might affect memory, anxiety-related behaviors, and the serum level of neurochemical markers such as brain-derived neurotrophic factor (BDNF) and corticosterone in a rat model. Materials and Methods:The disk-over-water (DOW) apparatus was employed to induce TSD and CPSR in male Wistar rats. The six study arms were as follows: cage control, 48 hours; cage control, seven days; DOW control, 48 hours; DOW control, seven days, TSD, and CPSR. Elevated plus-maze (EPM) was used to measure parameters (percentage of OAT, percentage of OAE, and locomotor activity) corresponding to anxiety and aversive memory. To measure serum BDNF and corticosterone levels using the ELISA method, blood samples were drawn from all rats on the fourth day at 5 P.M. Results: Our results demonstrated that TSD (P < 0.001) and CPSR (P < 0.001) induce memory impairment while exert anxiolytic-like effects in comparison with controls. Data showed that CPSR causes more memory impairment and anxiolytic-like effect in comparison to TSD (P < 0.001).These interventions however, did not alter the locomotor activity. Serum corticosterone level raised dramatically in CPSR rats in comparison to TSD and controls. Although the difference in serum BDNF level between TSD and CPSR arms was insignificant, it was markedly decreased in comparison to corresponding controls (P < 0.001). Conclusions: Our findings suggest the more pronounced effect of CPSR rather than TSD in impairing aversive memory and reducing anxiety. Decreased BDNF and peaked corticosterone level in TSD and CPSR suggest the probable inflammatory processes involved in possible insults to the brain caused by SD.

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“…The LC-NE system has been shown to be activated by a myriad of stressors. CRF and opioids are important mediators of the LC-NE system during stress [5]. Moreover, it is an integral site of CRF and opioid convergence that plays a vital role in the cognitive component of the stress response [25].…”

Section: Nih Public Accessmentioning

confidence: 99%

“…Both of these pathways have been implicated in both the stress response [22] and opiate actions [12]. Interestingly, the sensitivity of the LC-NE system to stress has been known to be regulated in part by CRF and opioids in a reciprocal fashion [5]. Recent evidence showing convergence of CRF-and ENK-immunoreactive axon terminals onto LC dendrites [19] support the reciprocal regulation of LC-NE system during stress.…”

Section: Nih Public Accessmentioning

confidence: 99%

Ultrastructural evidence for co-localization of corticotropin-releasing factor receptor and μ-opioid receptor in the rat nucleus locus coeruleus

Reyes

Glaser

Bockstaele

2007

Neuroscience Letters

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Previous studies have shown that corticotropin-releasing factor (CRF), an integral mediator of the stress response, and opioids regulate the activity of the locus-coeruleus-norepinephrine (LC-NE) system during stress in a reciprocal manner. Furthermore, repeated opiate exposure sensitizes noradrenergic neurons to CRF. Previous studies have shown that μORs are prominently distributed within somatodendritic processes of catecholaminergic neurons in the LC and axon terminals containing opioid peptides and CRF converge within the LC. To further examine cellular sites for interactions between CRF receptor type 1 (CRFr) and μOR, immunofluorescence and electron microscopic analysis of the rat LC was conducted. Triple immunofluorescence showed prominent co-localization of the CRFr and μOR in noradrenergic somata in the LC. Ultrastructural analysis confirmed dual localization of CRFr and μOR in common dendritic processes in the LC. Semiquantitative analysis showed that of the dendrites exhibiting CRFr immunolabeling, 57% expressed μOR immunoreactivity. These data provide ultrastructural evidence that CRFr and μOR are colocalized in LC neurons, a cellular substrate that may underlie opiate-induced sensitization of brain noradrenergic neurons to CRF. Keywordscorticotropin-releasing factor receptor 1; μ-opioid receptor; immunocytochemistry; electron microscopy Corticotropin-releasing factor (CRF), the hypothalamic neurohormone that initiates release of adrenocorticotropin in response to stress [20] also serves as a neurotransmitter that activates neurons of the noradrenergic nucleus locus coeruleus (LC). CRF administration increases the spontaneous discharge rate of LC neurons [21]. Microinfusion of CRF receptor antagonists into the LC abrogates increases in LC discharge activity elicited by both intracerebroventricularly (icv) administered CRF [6] and certain stimuli [24]. Likewise, hypotensive stress-induced activation of LC neurons is blocked by microinfusion of CRF directly into the LC [24]. Taken together, these data suggest that CRF release in the LC increases activity of noradrenergic neurons. In addition, CRF potently activates forebrain electroencephalographic (EEG) activity [7]. Consistent with physiological findings, Corresponding Author: Beverly A. S. Reyes, Ph.D., Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, PA 19107, Voice: (215) FAX: (215) 955-7921, e-mail: bsr103@jefferson.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The LC is densely innervated by process...

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Evidence for Functional Release of Endogenous Opioids in the Locus Ceruleus during Stress Termination

Cited by 86 publications

References 30 publications

Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress

Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress

Aversive Memory, Anxiety-Related Behaviors, and Serum Neurochemical Levels in a Rat Model of Labored Sleep Loss

Ultrastructural evidence for co-localization of corticotropin-releasing factor receptor and μ-opioid receptor in the rat nucleus locus coeruleus

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