δ-Opioid receptor immunoreactivity: Distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin

Ulf Arvidsson, Robert J. Dado, Maureen Riedl, Jang Hern Lee, Ping Y. Law, Horace H. Loh, Robert Elde, Martin W. Wessendorf

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Abstract

We have recently developed antisera which recognize epitopes of the cloned δ-opioid receptor (DOR; Dado et al., 1993). In the present report we have further characterized these antisera, and raised additional antisera in rats. We used these antisera to determine the distribution of DOR-like immunoreactivity (-LI) in rat spinal cord and brainstem in relation to serotoninergic, noradrenergic, and enkephalinergic neurons. We found DOR-LI in fibers and varicosities distributed throughout the spinal cord gray matter, with highest densities in the superficial dorsal horn, in autonomic regions, around the central canal as well as in the ventral horn motor nuclei. In the brainstem a dense innervation of DOR-immunoreactive (-IR) fibers was found in several nuclei such as spinal trigeminal nuclei, midline raphe nuclei, parabrachial nuclei, periaqueductal gray matter (PAG), interpeduncular nucleus, and substantia nigra. A group of DOR-positive cells was seen in the laterodorsal tegmental nucleus. In addition, a few DOR-IR cell bodies were demonstrated in the parabrachial nuclei, interpeduncular nucleus, PAG, and superior and inferior colliculi as well as around the central canal in the spinal cord. All DOR-positive cells showed a punctuate staining pattern within the cytoplasm of the cell body and in primary dendrites. No plasma membrane staining of cells or dendrites could be demonstrated using the DOR antisera. Double-labeling experiments for DOR and 5-hydroxytryptamine (5HT, serotonin) revealed that some 5HT-IR neurons in the raphe complex were surrounded by DOR-IR fibers. In the spinal cord a high degree of coexistence was found between DOR and 5HT in nerve fibers and varicosities in the neuropil around the motoneurons and in lamina V of the dorsal horn. In autonomic regions of the spinal cord, a low degree of colocalization was seen between DOR and 5HT; in the superficial dorsal horn no coexistence was found. Tyrosine hydroxylase (TH)-positive neurons in the brainstem (in the A5 area, locus coeruleus, and A7 area) were apposed by DOR- positive fibers. However, no coexistence could be seen between DOR and TH in any part of the spinal cord. A close relation, but no coexistence, was observed between DOR- and enkephalin (ENK)-IR fibers in the spinal cord ventral horn; in the intermediolateral nucleus a low degree of colocalization was observed. Thus, a δ-opioid receptor may affect the activity of descending serotoninergic and noradrenergic neurons by means of modulating the release of neurotransmitters from afferents to these neurons. In addition, δ-opioid receptors appear poised to modulate the release of 5HT (and coexisting peptides) from fibers in the spinal cord ventral horn and lamina V. However, these receptors appear unlikely to be importantly involved in modulation of the release of catecholamines or enkephalin in the spinal cord, or in modulation of the release of 5HT in the superficial dorsal horn. Finally, these data suggest that the antisera used preferentially localize a δ-opioid receptor which is targeted to the axonal compartment of neurons, and thus this receptor most likely functions at a presynaptic site.

Original languageEnglish (US)
Pages (from-to)1215-1235
Number of pages21
JournalJournal of Neuroscience
Volume15
Issue number2
DOIs
StatePublished - Feb 1995

Keywords

  • 5-hydroxytryptamine
  • coexistence
  • compartmentalization
  • dorsal horn
  • intermediolateral cell column
  • motoneurons
  • noradrenergic nuclei
  • opioid receptor
  • opioids
  • presynaptic receptor
  • raphe nuclei
  • tyrosine hydroxylase

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