Alpha1‐adrenergic Effects on Dopamine Neurons Recorded Intracellularly in the Rat Midbrain Slice

Johan Grenhoff, R. Alan North, Steven W. Johnson

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10–100 μM) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100–1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin‐induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58% of all principal neurons and had no effect in 42%; this effect was mimicked by the α‐adrenergic agonist phenylephrine (10–30 μM) which depolarized 43 of 72 cells. The α1 receptor antagonist prazosin (30–100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas α2‐ and β‐adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at ‐60 mV) and reduced cord conductance by 0.81 ± 0.14 nS (n= 4). Inward current evoked by phenylephrine became outward at ‐96 ± 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABAA receptor‐mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of α1‐adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynaptic potentials evoked by stimulation of α1‐adrenergic receptors located on local interneurons.

Original languageEnglish (US)
Pages (from-to)1707-1713
Number of pages7
JournalEuropean Journal of Neuroscience
Volume7
Issue number8
DOIs
StatePublished - Aug 1995

Keywords

  • interneuron
  • noradrenalin
  • phenylephrine
  • potassium current
  • substantia nigra
  • ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

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