5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT(2C), 5-HT(4) and 5-HT(1A) receptors.
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 microM, 180+/-16.8%, n=35) with an estimated EC(50) of 5.4 microM. The non-specific 5-HT(2) receptor agonist alpha-methyl 5-HT (1-10 microM) mimicked 5-HT induced excitations (15 cells). These excitations were significantly reduced by pre-perfusion with the specific 5-HT(2C) receptor antagonist RS102221 (500 nM, 9 cells) and the 5HT(4) 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-HT(1A) antagonist WAY100135 (1 microM, 4 cells). No inhibitory responses were observed following alpha-methyl 5-HT applications. Both the excitations and inhibitions were unaffected by picrotoxin (50 microM, n=5) and CNQX (10 microM, 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-HT(4) receptors and the second an inhibition which is mediated by 5-HT(1A) receptors.
Stanford
I M
IM
School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. i.m.stanford@aston.ac.uk
Kantaria
M A
MA
Chahal
H S
HS
Loucif
K C
KC
Wilson
C L
CL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4 / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D020531:Subthalamic Nucleus / Q000166:cytology / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin