Comparison between δ-opioid receptor functional response and autoradiographic labeling in rat brain and spinal cord

Amynah Amir Ali Pradhan, Paul Brian Sydenham Clarke

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The distribution of δ-opioid receptors (DORs) in the rat central nervous system has been previously characterized by radioligand binding and immunohistochemistry. However, the functional neuroanatomy of DORs has not been mapped in any detail; this is potentially important, because these receptors appear to be primarily cytosolic. Opioid receptors can couple to Gi/o G proteins, a process that is detected by agonist-stimulated [ 35S]guanylyl-5′-O-(γ-thio)-triphosphate ([ 35S]GTPγS) binding. The purpose of this study was therefore to determine the distribution of functional DORs, as assessed by [ 35S]GTPγS autoradiographic labeling in response to the DOR agonist deltorphin II. For comparison, adjacent sections were labeled with [125I]deltorphin II or the DOR antagonist [125I]AR- M100613. In all three assays, μ-opioid receptors were blocked pharmacologically. The distributions of [125I]deltorphin II and [125I]AR-M100613 were highly correlated but not identical. Deltorphin II increased [35S]GTPγS binding in a concentration-dependent and naltrindole-sensitive manner. The regional [35S]GTPγS response to deltorphin II was only moderately predicted by agonist or antagonist radioligand binding (r = 0.67 and 0.50, respectively). [35S] GTPγS responses to deltorphin II were strongest in the extended striatum (caudate putamen, nucleus accumbens, olfactory tubercle) and cerebral cortex. In contrast, some areas reported to mediate DOR analgesia (brainstem, spinal cord) possessed a much lower [35S]GTPγS response. These findings demonstrate the existence of a partial mismatch between DOR radioligand binding and [35S]GTPγS response. This divergence possibly reflects regional heterogeneity in G-protein receptor coupling, or in the subcellular localization of DOR.

Original languageEnglish
Pages (from-to)416-426
Number of pages11
JournalJournal of Comparative Neurology
Volume481
Issue number4
DOIs
StatePublished - Jan 24 2005

Keywords

  • Analgesia
  • Opiates
  • Receptor localization
  • Reward

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