Receptor binding and mRNA for many of the characterised 5-HT receptors have been found in basal ganglia. Of particular interest are 5-HT_1A and 5-HT_2C receptors, which have previously been reported to have potential therapeutic benefit in Parkinson’s disease (Nicholson & Brotchie, 2002). Thus, antagonists of the 5-HT_1Areceptor suppress L-DOPA induced dyskinesia in animal models and Parkinson’s patients while antagonist action at 5-HT_2C receptors reduce motor side-effects, especially orofacial dyskinesias and turning behaviour. Furthermore, there appears to be up-regulation of 5-HT_2C receptors and down-regulation of 5-HT_1A receptors in the dopamine depleted state. Here, we use single unit extracellular recordings in a brain slice preparation to determine the effects of exogenously applied 5-HT on single STN neurones and to pharmacologically characterise the 5-HT receptor subtypes involved. 300μm thick sagittal and parasagittal slices were obtained from 30- to 40-day-old CB57BL/6JCrL mice. The animals were anaesthetised with 4% fluorothane in O₂ and humanely killed. Slices were perfused at 2-3ml/min with aCSF containing (mM) NaCl 126, KCl 2.5, NaH₂PO₄ 1.2, MgCl₂ 1.3, CaCl₂ 2.4, glucose 10, buffered to pH 7.4 with NaHCO₃(26mM) saturated with 95% O₂-5% CO₂. Single unit extracellular recordings were made using glass microelectrodes filled with 2M NaCl of resistance ~10MΩ. All data are expressed as mean±S.E.M. and a paired t test used to test for statistical significance. Recordings were made from 35 STN neurones. These cells fired action potentials at a rate of 8.4 ±0.7Hz in a mostly regular manner. In 28 cells (80%), 5-HT application increased STN firing rate (10μM, 172 ± 18.6%) with an estimated EC₅₀ value of 6.5μM. No changes in firing pattern were observed. The excitation was mimicked by the non-specific 5-HT₂ receptor agonist α-methyl 5-HT (1-10μM, 11 cells). Excitations were significantly reduced by prior 15-min perfusion with the specific 5-HT_2C receptor antagonist RS 102221 (500nM). RS 1002221 (500nM) also reduced the excitatory effect of α-methyl 5-HT (3μM). In 5 cells (14%), 5-HT induced a biphasic response of excitation followed by inhibition which also appeared concentration-dependent, while in 2 cells (6%) inhibition alone was observed. No inhibitions were observed on α-methyl 5-HT applications. Both the excitations and inhibitions were unaffected by CNQX (10μM) and picrotoxin (50μM). In summary, the excitation induced by 5-HT in STN neurones appears to be a direct effect mediated by 5-HT_2C receptors although inhibitions possibly mediated by the 5-HT_1A receptor subtype are evident.