Noradrenergic modulation of the hyperpolarization-activated cation current (Ih) in dopamine neurons of the ventral tegmental area

F. Arencibia-Albite, C. Paladini, J. T. Williams, C. A. Jiménez-Rivera

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41 Scopus citations

Abstract

Alterations in the state of excitability of midbrain dopamine (DA) neurons from the ventral tegmental area (VTA) may underlie changes in the synaptic plasticity of the mesocorticolimbic system. Here, we investigated norepinephrine's (NE) regulation of VTA DA cell excitability by modulation of the hyperpolarization-activated cation current, Ih, with whole cell recordings in rat brain slices. Current clamp recordings show that NE (40 μM) hyperpolarizes spontaneously firing VTA DA cells (11.23±4 mV; n=8). In a voltage clamp, NE (40 μM) induces an outward current (100±24 pA; n=8) at -60 mV that reverses at about the Nernst potential for potassium (-106 mV). In addition, NE (40 μM) increases the membrane cord conductance (179±42%; n=10) and reduces Ih amplitude (68±3% of control at -120 mV; n=10). The noradrenergic α-1 antagonist prazosin (40 μM; n=5) or the α-2 antagonist yohimbine (40 μM; n=5) did not block NE effects. All NE-evoked events were blocked by the D2 antagonists sulpiride (1 μM) and eticlopride (100 nM) and no significant reduction of Ih took place in the presence of the potassium channel blocker BaCl2 (300 μM). Therefore, it is concluded that NE inhibition of Ih was due to an increase in membrane conductance by a nonspecific activation of D2 receptors that induce an outward potassium current and is not a result of a second messenger system acting on h-channels. The results also suggest that Ih channels are mainly located at dendrites of VTA DA cells and, thus, their inhibition may facilitate the transition from single-spike firing to burst firing and vice versa.

Original languageEnglish (US)
Pages (from-to)303-314
Number of pages12
JournalNeuroscience
Volume149
Issue number2
DOIs
StatePublished - Oct 26 2007

Keywords

  • I
  • VTA
  • adrenergic receptors
  • dopamine receptors
  • norepinephrine

ASJC Scopus subject areas

  • Neuroscience(all)

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