Tyramine excites rat subthalamic neurons in vitro by a dopamine-dependent mechanism

Zi Tao Zhu, Adam C. Munhall, Steven W. Johnson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Tyramine, an endogenous ligand for mammalian trace amine-associated receptors, may act as a neuromodulator that regulates neuronal activity in basal ganglia. Using whole-cell patch recordings of subthalamic nucleus (STN) neurons in rat brain slices, we found that bath application of tyramine evoked an inward current in voltage-clamp in over 60% of all STN neurons. The inward current induced by tyramine was mimicked by the D2-like dopamine receptor agonist quinpirole, but was only partially blocked by the D2-like receptor antagonist sulpiride. In contrast, the D1-like receptor agonist SKF38393 evoked no current in STN neurons. Inward current evoked by tyramine was significantly reduced by the catecholamine uptake inhibitor nomifensine, and by exhausting catecholamines in the brain via pretreatment with reserpine. Tyramine also reduced the amplitude of GABAA receptor-mediated IPSCs that were evoked by focal electrical stimulation of the slice. Inhibition of IPSCs by tyramine was mimicked by quinpirole and was blocked by sulpiride but not by SCH23390, a D1 receptor antagonist. Moreover, tyramine-induced inhibition of IPSCs was reduced in slices pretreated with reserpine, and this inhibition could be restored by briefly superfusing the slice with dopamine. These results suggest that tyramine acts as an indirect dopamine agonist in the STN. Although inhibition of IPSCs is mediated by D2-like receptors, the dopamine-dependent inward currents evoked by tyramine do not fit a typical dopamine receptor pharmacological profile.

Original languageEnglish (US)
Pages (from-to)1169-1178
Number of pages10
Issue number4
StatePublished - Mar 2007
Externally publishedYes


  • Brain slices
  • Dopamine
  • Electrophysiology
  • Inward current
  • Subthalamic neurons
  • Subthalamic nucleus
  • Synaptic current
  • Trace amine
  • Tyramine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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