Excitatory effects of dopamine on subthalamic nucleus neurons: In vitro study of rats pretreated with 6-hydroxydopamine and levodopa

Zitao Zhu, Muriel Bartol, Kezhong Shen, Steven W. Johnson

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Increased output from the subthalamic nucleus (STN) following chronic dopamine depletion has been linked to the rigidity and tremor seen in Parkinson's disease (PD). We used extracellular microelectrode recordings from rat brain slices to investigate effects of dopamine on STN neurons. In brain slices prepared from rats that received unilateral 6-hydroxydopamine (6-OHDA) treatment, the spontaneous firing rate of STN neurons was reduced by 63%, and the firing pattern was more irregular, compared to STN neurons from normal rats. However, treatment with levodopa (50 mg/kg, i.p., daily) for 4 weeks normalized the firing rate and pattern of STN neurons in the 6-OHDA-treated rats. Dopamine (3-300 μM), added to the superfusate, significantly increased the firing rates of STN neurons in a concentration-dependent fashion, and also produced a more regular firing pattern in 6-OHDA-lesioned tissue. This excitatory effect of dopamine was mimicked by a D2 receptor agonist (quinpirole), and was reduced by the D2 antagonists haloperidol, clozapine and sulpiride. Antagonists of the D1 receptor (SCH-23390) and ionotropic glutamatergic receptors (CNQX and AP5) could not block the effect of dopamine on firing rate. These results suggest that dopamine exerts a direct excitatory influence on STN neurons via the activation of D2-like receptors.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalBrain research
Volume945
Issue number1
DOIs
StatePublished - Jul 26 2002

Keywords

  • Dopamine
  • Electrophysiology
  • In vitro
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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