Dynorphin-containing axons directly innervate noradrenergic neurons in the rat nucleus locus coeruleus

Reyes, Beverly A.S.; Johnson, Anthony; Glaser, Julia; Commons, Kathryn G.; Bockstaele, Elisabeth J. Van

doi:10.1016/j.neuroscience.2006.12.056

Cited by 45 publications

(59 citation statements)

References 77 publications

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“…The locus coeruleus (LC) is one of the primary sources of norepinephrine (NE) in the forebrain [81] . Dynorphin and κ opioid receptors are coexpressed within the LC on noradrenergic (NA) neurons [67,[82][83][84][85] . Previous reports have shown that both stress and CRF engage in LC NA cell firing [86,87] .…”

Section: Brain Regions Involved In κ Opioid Receptor-mediated Anxietymentioning

confidence: 99%

The role of the dynorphin/κ opioid receptor system in anxiety

Hang

Wang

et al. 2015

Acta Pharmacol Sin

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Anxiety disorders are the most common and prevalent forms of psychiatric disease, although the biological basis of anxiety is not well understood. The dynorphin/κ opioid receptor system is widely distributed in the central nervous system and has been shown to play a critical role in modulating mood and emotional behaviors. In the present review, we summarize current literature relating to the role played by the dynorphin/κ opioid receptor system in anxiety and κ opioid receptor antagonists as potential therapeutic agents for the treatment of anxiety disorders.

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Section: Brain Regions Involved In κ Opioid Receptor-mediated Anxietymentioning

confidence: 99%

The role of the dynorphin/κ opioid receptor system in anxiety

Hang

Wang

et al. 2015

Acta Pharmacol Sin

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“…The specificity of ppDYN antiserum was tested by absorption controls with the cognate peptides (Arvidsson et al, 1995;Reyes et al, 2007). Preabsorption of ppDYN with the antigenic peptide at 1 μM blocked the immunoreactivity in regions known to express DYN (hippocampus, spinal cord).…”

Section: Specificity Of Antiseramentioning

confidence: 99%

“…Additionally, kappa opioid receptor (κ-OR) antagonists prevent stress-elicited behaviors that are endpoints of depression such as immobility in the forced swim test and passive behavior in learned helplessness (Mague et al, 2003;McLaughlin et al, 2003;Shirayama et al, 2004). Our recent evidence for DYN-immunoreactive terminals targeting tyrosine hydroxylase (TH)-immunoreactive perikarya and processes in the LC (Reyes et al, 2007) showed that the majority of synaptic specializations observed were asymmetric synapses suggesting coexisting excitatory transmitters such as glutamate or CRF. These data have compelled us to consider the impact of this additional opioid peptide family in our model of co-regulation of the LC system by endogenous opioids and the stress peptide, CRF.…”

Section: Introductionmentioning

confidence: 99%

Dynorphin and stress‐related peptides in rat locus coeruleus: Contribution of amygdalar efferents

Reyes

Drolet

Bockstaele

2008

J of Comparative Neurology

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The interaction between the stress axis and endogenous opioid systems has gained substantial attention as it is increasingly recognized that stress alters individual sensitivity to opiates. One site at which opiates and stress substrates may interact to have global effects on behavior is within the locus coeruleus (LC). We have previously described interactions of several opioid peptides (e.g. pro-opiomelanocortin, enkephalin) with the stress-related peptide, corticotropin-releasing factor (CRF) in the LC. To further examine interactions between DYN, ENK and CRF in the LC, sections were processed for detection of DYN, CRF or DYN and ENK in rat brain. DYN-and CRF-containing axon terminals overlapped noradrenergic dendrites in this region. Dual immunoelectron microscopy showed coexistence of DYN and CRF with 35% of axon terminals containing DYN that were also immunoreactive for CRF. In contrast, few axon terminals contained both DYN and ENK. A potential DYN/CRF afferent is the central nucleus of the amygdala (CeA). Dual in situ hybridization showed that in CeA neurons, 31% of DYN mRNApositive cells co-localized with CRF mRNA while 53% of CRF mRNAcontaining cells colocalized with DYN mRNA. Finally, to determine whether limbic DYN afferents target the LC, the CeA was electrolytically lesioned. Light-level densitometry of DYN labeling in the LC showed a significant decrease in immunoreactivity on the side of the lesion. Taken together, these data indicate that DYN-and CRF-labeled axon terminals, most likely arising from amygdalar sources are positioned to dually impact LC function whereas DYN and ENK function in parallel.

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“…Recently, LC innervation by the -OR ligand, dynorphin, was identified (Reyes et al, 2007) and others have demonstrated -OR mRNA and protein in the LC (DePaoli et al, 1994;Mansour et al, 1994), suggesting that this system regulates LC activity. This is of particular interest as dynorphin and -ORs are implicated in stress-related disorders (Pliakas et al, 2001;Mague et al, 2003;McLaughlin et al, 2006a).…”

Section: Introductionmentioning

confidence: 99%

Presynaptic Inhibition of Diverse Afferents to the Locus Ceruleus by -Opiate Receptors: A Novel Mechanism for Regulating the Central Norepinephrine System

Kreibich¹,

Reyes²,

Curtis³

et al. 2008

Journal of Neuroscience

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The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at -opiate receptors. Because the LC is also innervated by the endogenous -opiate receptor (-OR) ligand dynorphin and expresses -ORs, this study investigated -OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of -ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the -OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the -OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that -ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate -ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

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Dynorphin-containing axons directly innervate noradrenergic neurons in the rat nucleus locus coeruleus

Cited by 45 publications

References 77 publications

The role of the dynorphin/κ opioid receptor system in anxiety

The role of the dynorphin/κ opioid receptor system in anxiety

Dynorphin and stress‐related peptides in rat locus coeruleus: Contribution of amygdalar efferents

Presynaptic Inhibition of Diverse Afferents to the Locus Ceruleus by -Opiate Receptors: A Novel Mechanism for Regulating the Central Norepinephrine System

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