Opioid circuits originating from the nucleus paragigantocellularis and their potential role in opiate withdrawal

Johnson, Anthony; Peoples, James; Stornetta, Ruth L.; Bockstaele, Elisabeth J. Van

doi:10.1016/s0006-8993(02)03367-x

Cited by 32 publications

(20 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of considerable interest in this study was the finding of a dense innervation in the brainstem of both the dorsal vagal complex and the Amb/ VLM region. The findings of this study extend the observations of several retrograde tract-tracing studies showing labeled neurons throughout the MARN after injections that were located in dorsal vagal complex Johnson et al, 2002;Millhorn et al, 1987;Ross et al, 1981;Thor and Helke, 1987;Zelman et al, 1984) or in the region of the nucleus ambiguus at sites identified as containing ventral medullary respiratory neurons (Ellenberger and Feldman, 1990;Holtman and Speck, 1994;Smith et al, 1989).…”

Section: Discussionsupporting

confidence: 89%

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Babic

Ciriello

2004

J of Comparative Neurology

View full text Add to dashboard Cite

The rostral ventromedial medulla (RVMM) is a sympathoexcitatory area. However, little is known about its efferent projections. In this study, biotinylated dextran amine (BDA) or Phaseolus vulgaris leucoagglutinin (PHA-L) were used to investigate the medullary and spinal cord projections from pressor sites in RVMM. Initially, RVMM was systematically explored in urethane-anesthetized rats using microinjection of L-glutamate for sites that elicited increases in arterial pressure. A pressor area was identified that included the rostral magnocellular reticular and rostral lateral paragigantocellular reticular nuclei. In the second series of experiments, BDA or PHA-L was iontophoretically injected into RVMM pressor sites. Anterograde labeling was observed throughout the brainstem and spinal cord, bilaterally, but with an ipsilateral predominance. Dense labeling was observed within the nucleus of the solitary tract (NTS); the greatest density of labeling was observed in the caudal dorsolateral, medial, and ventrolateral subnuclei. Additionally, light to moderately dense labeling was found within the nucleus substantia gelatinosus and commissural nucleus. In the nucleus ambiguus/ventrolateral medullary (Amb/VLM) region, the density of labeling was greatest in caudal regions. Within Amb, most of the labeling was localized to its external formation. Anterograde labeling was also found throughout the spinal cord. In the thoracolumbar segments, dense axonal labeling was observed within the dorsolateral funiculus. These labeled axons innervated the intermediolateral nucleus and the central autonomic area. Taken together, these data suggest that RVMM neurons elicit increases in sympathetic activity by likely providing a direct excitatory input to spinal sympathetic preganglionic neurons, and by a direct inhibitory input to medullary cardioinhibitory and depressor areas.

show abstract

Section: Discussionsupporting

confidence: 89%

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Babic

Ciriello

2004

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…There is general consensus that LC neurons are hyperactive during withdrawal (Aghajanian, 1978). Enhanced synaptic drive (e.g., strengthening of excitatory afferents onto LC neurons (Johnson et al, 2002) and intrinsic upregulation of neuronal excitability (Lane-Ladd et al, 1997;Han et al, 2006) have been implicated in the hyperactivity of the LC. Nevertheless, the relevance of this hyperactivity to withdrawal behavior remains controversial (Christie et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Absence and Rescue of Morphine Withdrawal in GIRK/Kir3 Knock-out Mice

Cruz¹,

Berton²,

Sollini³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

Although morphine induces both analgesia and dependence through -opioid receptors (MORs), the respective contributions of the intracellular effectors engaged by MORs remain unknown. To examine the contribution of G-protein-gated inwardly rectifying K ϩ (GIRK, Kir3) channels to morphine dependence and analgesia, we quantified naloxone-precipitated withdrawal behavior and morphine analgesia using GIRK knock-out ( Ϫ/Ϫ ) mice. The morphine withdrawal syndrome was strongly attenuated, whereas morphine analgesia was mostly preserved in mice lacking both GIRK2 and GIRK3 (GIRK2/3 Ϫ/Ϫ mice). In acute slices containing the locus ceruleus (LC) from GIRK2/3 Ϫ/Ϫ mice, the increase in spontaneous firing typically associated with morphine withdrawal was absent. Moreover, although morphine elicited normal presynaptic inhibition in the LC, postsynaptic GIRK currents were completely abolished in GIRK2/3 Ϫ/Ϫ mice. Altogether, these data suggested that morphine-evoked postsynaptic inhibition of the LC was required for the induction of dependence. Consistent with this hypothesis, morphine withdrawal behavior was rescued in GIRK2/3 Ϫ/Ϫ mice by ablation of adrenergic fibers using the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine. Our data suggest that inhibition of adrenergic tone is required for the induction of dependence, and that channels containing GIRK2 and GIRK3 serve as an inhibitory gate.

show abstract

“…Neurons in this region of the medullary reticular formation can respond to a diverse array of arousing inputs (Van Bockstaele et al, 1989) including, for example, changes in carbon dioxide tension or blood pressure in the service of cardiovascular and respiratory regulation (de-Oliveira et al, 1996;Lacerda et al, 2003;Schreihofer and Guyenet, 2003), painful stimuli Mason, 1998, 1999), and sexually relevant inputs (Marson and McKenna, 1990;Hubscher and Johnson, 1996;Yanagimoto et al, 1996;McKenna, 2001) from the pelvic nerve. Outputs from the nucleus paragigantocellularis and from the rostral ventrolateral medulla (RVLM), for example, have obvious import for arousal through their projections to locus coeruleus and other sites (Guyenet and Young, 1987;Huangfu et al, 1992;Johnson et al, 2002). Important roles for this part of the brainstem reticular formation, especially the RVLM, in cardiovascular and respiratory regulation have been established firmly (e.g., Guyenet et al, 1996;Schreihofer et al, 2000;Monnier et al, 2003;Weston et al, 2004).…”

Section: Ascending Influences From the Arousal Crescentmentioning

confidence: 99%

Generalized arousal of mammalian central nervous system

Pfaff

Westberg

Kow

2005

J of Comparative Neurology

View full text Add to dashboard Cite

A fundamental capacity of the mammalian CNS is becoming amenable to study with the techniques of functional genomics. Emphasized in this review are ascending connections from the medullary reticular formation and descending connections from the paraventricular nucleus of the hypothalamus. In particular, sex hormone effects on neurons allow us to relate generalized arousal to a specific form of arousal which is required for reproductive behaviors.

show abstract

Opioid circuits originating from the nucleus paragigantocellularis and their potential role in opiate withdrawal

Cited by 32 publications

References 77 publications

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Medullary and spinal cord projections from cardiovascular responsive sites in the rostral ventromedial medulla

Absence and Rescue of Morphine Withdrawal in GIRK/Kir3 Knock-out Mice

Generalized arousal of mammalian central nervous system

Contact Info

Product

Resources

About