Opioid-mediated regulation of A11 diencephalospinal dopamine neurons: Pharmacological evidence of activation by morphine

Samuel S. Pappas, Tom Kennedy, John L. Goudreau, Keith J. Lookingland

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Dopamine (DA) neurons of the A11 diencephalospinal system represent the sole source of DA innervation to the spinal cord in mice, serving neuromodulatory roles in the processing of nociceptive input and movement. These neurons originate in the dorso-caudal diencephalon and project axons unilaterally throughout the rostrocaudal extent of the spinal cord, terminating predominantly in the dorsal horn. The density of A11 DA axon terminals in the lumbar region is greater in males compared to females, while in both sexes the activity of neurons terminating in the thoracic spinal cord is greater than those terminating in the lumbar region. The present study was designed to test the hypothesis that A11 DA neurons are activated by opioids. To test this hypothesis, male and female mice were systemically treated with agonists or antagonists acting at the μ-opioid receptor, and spinal cord concentrations of DA and its metabolite DOPAC were determined in the thoracic and lumbar spinal cord using high performance liquid chromatography coupled with electrochemical detection. Systemic administration of the μ-opioid agonist morphine led to a dose- and time-dependent increase in spinal cord DOPAC/DA ratio (an estimate of DA neuronal activity) in both male and female mice, with greater changes occurring in the lumbar segment. Blockade of opioid receptors with the opioid antagonist naloxone reversed the stimulatory effects of morphine on A11 DA neurons in both male and female mice, but had little to no effect on the activity of these neurons when administered alone. Present findings are consistent with the conclusion that spinal cord-projecting axon terminals of A11 DA neurons are activated by opioids in both male and female mice, most likely through a dis-inhibitory mechanism.

Original languageEnglish (US)
Pages (from-to)614-621
Number of pages8
Issue number4
StatePublished - Sep 2011
Externally publishedYes


  • A11
  • Diencephalospinal
  • Dopamine
  • Morphine
  • Spinal cord
  • μ-opioids

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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