5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT2C, 5-HT4 and 5-HT1A receptors

I.M. Stanford*, M.A. Kantaria, H.S. Chahal, K.C. Loucif, C.L. Wilson

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Extracellular single-unit recordings in mouse brain slices were used to determine the effect of exogenously applied 5-HT on STN neurones. Recordings were made from 74 STN cells which fired action potentials at a regular rate of 7.19 ± 0.5 Hz. In 61 cells (82%), 5-HT application increased STN neurone firing rate (10 μM, 180 ± 16.8%, n = 35) with an estimated EC 50 of 5.4 μM. The non-specific 5-HT2 receptor agonist α-methyl 5-HT (1-10 μM) mimicked 5-HT induced excitations (15 cells). These excitations were significantly reduced by pre-perfusion with the specific 5-HT2C receptor antagonist RS102221 (500 nM, 9 cells) and the 5HT4 antagonist GR113808 (500 nM, 7 cells). In 6 cells (8%) 5-HT induced biphasic responses where excitation was followed by inhibition, while in 7 cells (9%) inhibition of firing rate was observed alone. Inhibitory responses were reduced by the 5-HT1A antagonist WAY100135 (1 μM, 4 cells). No inhibitory responses were observed following α-methyl 5-HT applications. Both the excitations and inhibitions were unaffected by picrotoxin (50 μM, n = 5) and CNQX (10 μM, n = 5) indicative of direct postsynaptic effects. Thus, in STN neurones, 5-HT elicits two distinct effects, at times on the same neurone, the first being an excitation which is mediated by 5-HT 2C and 5-HT4 receptors and the second an inhibition which is mediated by 5-HT1A receptors. © 2005 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1228-1234
Number of pages7
JournalNeuropharmacology
Volume49
Issue number8
DOIs
Publication statusPublished - Dec 2005

Keywords

  • α-methyl-5-HT
  • basal ganglia
  • GR113808
  • RS102221
  • single unit
  • WAY100135
  • alpha-methyl-5-HT

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