Excitation by dopamine of rat subthalamic nucleus neurones in vitro - A direct action with unconventional pharmacology

A. Tofighy, A. Abbott, D. Centonze, A. J. Cooper, E. Noor, S. M. Pearce, M. Puntis, I. M. Stanford, M. A. Wigmore, M. G. Lacey

Research output: Contribution to journalArticle

Abstract

Recent anatomical and physiological studies have pointed to a functional innervation of the subthalamic nucleus by dopamine. This nucleus has a pivotal role in basal ganglia function and voluntary movement control and the possibility that dopamine, and dopaminergic medication used in Parkinson's disease, might directly influence its activity is of considerable interest. We have evaluated electrophysiologically the action and pharmacology of dopamine on single subthalamic neurones in rat brain slices. Dopamine increased firing rate to up to a mean of 60% in 98% of the 261 neurones tested when examined using extracellular single-unit recording. This excitation was unaffected by the GABA antagonist picrotoxin, and the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, and persisted in a low Ca2+/raised Mg2+ solution, indicative of a direct action, independent of synaptic transmission. Of the 33 cells examined using whole patch-clamp recording, only 13 showed measurable increases in firing rate and/or depolarisations in response to dopamine. Dopamine-responsive cells displayed significantly greater access resistance, suggesting that an unidentified cytoplamic constituent, removed by whole-cell dialysis, was required for the response. Using extracellular recording, the D2-like dopamine receptor agonists quinpirole and bromocryptine, but not the D1-like receptor agonist 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol, also consistently caused an excitation. This was mimicked by the catecholamine releaser amphetamine in 60% of cells tested. However, the dopamine excitation was not significantly reduced either by the D1-like receptor antagonist 7-chloro8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine or the D2-like receptor antagonists (-)-sulpiride, eticlopride and (+)-butaclamol, and the quinpirole excitation was also unaffected by (-)-sulpiride. In contrast, (-)-sulpiride, eticlopride and (+)-butaclamol all abolished the D2-like receptor-mediated inhibition by dopamine of substantia nigra pars compacta neurones. The α-adrenoceptor antagonist phentolamine was a weak antagonist of dopamine excitations, but not of those caused by quinpirole. Dopamine excitations also showed weak sensitivity to the 5-HT2 antagonist ritanserin, but were unaffected by the α1-adrenoceptor antagonist prazocin and the β-adrenoceptor antagonist propranolol. The pharmacology of this dopamine excitation is inconsistent with an action on any known catecholamine receptor. However, the effect of amphetamine indicates that an unidentified monamine - possibly dopamine - can be released within the subthalamic nucleus to cause an excitation. The anomalies of its pharmacological characterisation do not strongly support a physiologically relevant direct action of dopamine in the rat subthalamic nucleus.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalNeuroscience
Volume116
Issue number1
DOIs
Publication statusPublished - Jan 15 2003

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Keywords

  • Adrenoceptors
  • Basal ganglia
  • Brain slices
  • Dopamine receptors
  • Single unit recording
  • Whole-cell patch clamp

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tofighy, A., Abbott, A., Centonze, D., Cooper, A. J., Noor, E., Pearce, S. M., Puntis, M., Stanford, I. M., Wigmore, M. A., & Lacey, M. G. (2003). Excitation by dopamine of rat subthalamic nucleus neurones in vitro - A direct action with unconventional pharmacology. Neuroscience, 116(1), 157-166. https://doi.org/10.1016/S0306-4522(02)00546-8