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.