Noradrenergic inhibition of midbrain dopamine neurons

Carlos A. Paladini, John T. Williams

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Receptors that couple to phosphoinositide hydrolysis, which include metabotropic glutamate receptors (mGluRs) and muscarinic receptors, are known to either activate or inhibit the activity of dopamine cells depending on the pattern of receptor activation. Transient activation of α1 adrenoceptors with norepinephrine (NE) resulted in an outward current in midbrain dopamine neurons recorded in brain slices. The NE-mediated outward current was induced by activation of a potassium conductance through release of calcium from intracellular stores. Unlike the mGluR-mediated outward current, the outward current induced by α1 adrenoceptors often consisted of multiple peaks. Activation of α1 adrenoceptors also induced a wave of calcium release that spread through the soma and proximal dendrites without a decline in amplitude or rate of propagation and therefore differed qualitatively from that induced by mGluRs. Finally, the α1 adrenoceptor-activated outward current was more sensitive to the calcium store-depleting agents ryanodine and caffeine. Thus, although both α1 adrenoceptors and mGluRs mobilize calcium from intracellular stores, the mechanisms and pools of calcium differ. The results suggest that noradrenergic innervation of dopamine cells can directly inhibit the activity of dopamine cells. Psychostimulants, such as amphetamine, will therefore have a direct effect on the firing pattern of dopamine neurons through a combination of actions on dopamine and α1 adrenoceptor activation.

Original languageEnglish (US)
Pages (from-to)4568-4575
Number of pages8
JournalJournal of Neuroscience
Issue number19
StatePublished - May 12 2004


  • Calcium
  • Inositol trisphosphate
  • Metabotropic
  • Ryanodine
  • mGluR
  • sK
  • α adrenoceptor

ASJC Scopus subject areas

  • Neuroscience(all)


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