Contribution of dopamine receptors to periaqueductal gray-mediated antinociception

Paul J. Meyer, Michael M. Morgan, Laura B. Kozell, Susan L. Ingram

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Rationale: Morphine relieves pain, in part, by acting on neurons within the periaqueductal gray (PAG). Given that the PAG contains a subpopulation of dopamine neurons, dopamine may contribute to the antinociceptive effects mediated by the PAG. Methods: This hypothesis was tested by measuring the behavioral and electrophysiological effects of administering dopamine agonists and antagonists into the ventrolateral PAG (vPAG). An initial histological experiment verified the existence of dopamine neurons within the vPAG using dopamine transporter and tyrosine hydroxylase antibodies visualized with confocal microscopy. Results: Microinjection of cumulative doses of morphine into the vPAG caused antinociception that was dose-dependently inhibited by the dopamine receptor antagonist α-flupenthixol. α-Flupenthixol had no effect on nociception when administered alone. Injection of the dopamine receptor agonist (-) apomorphine into the vPAG caused a robust antinociception that was inhibited by the D2 antagonist eticlopride but not the D1 antagonist SCH-23390. The effects of dopamine on GABAA-mediated evoked inhibitory post-synaptic potentials (eIPSCs) were measured in PAG slices. Administration of met-enkephalin inhibited peak eIPSCs by 20-50%. Dopamine inhibited eIPSCs by approximately 20-25%. Administration of α-flupenthixol (20 μM) attenuated eIPSC inhibition by dopamine but had no effect on met-enkephalin-induced inhibition. Conclusions: These data indicate that PAG dopamine has a direct antinociceptive effect in addition to modulating the antinociceptive effect of morphine. The lack of an effect of α-flupenthixol on opioid-inhibition of eIPSCs indicates that this modulation occurs in parallel or subsequent to inhibition of GABA release.

Original languageEnglish (US)
Pages (from-to)531-540
Number of pages10
Issue number3
StatePublished - Jun 2009
Externally publishedYes


  • Analgesia
  • Biogenic amine
  • Catecholamine
  • Descending modulation
  • Drug addiction
  • Immunohistochemistry
  • Opiate
  • Opioid receptor
  • Pain
  • Patch-clamp electrophysiology

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Contribution of dopamine receptors to periaqueductal gray-mediated antinociception'. Together they form a unique fingerprint.

Cite this