The subthalamic nucleus is innervated by 5-HT afferents from the dorsal raphe nucleus and expresses high density of 5-HT(2C) receptors. However, the role of these receptors in neuronal firing of subthalamic neurons in vivo is unknown. In the present study, we examined the changes in the firing rate and firing pattern of subthalamic neurons, and the effect of the nonselective 5-HT(2C) receptor agonist m-CPP and selective antagonist SB242084 on the neuronal firing of subthalamic neurons in normal rats, sham rats, and rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta by using extracellular recording. Results showed an increase in the percentage of subthalamic neurons exhibiting burst-firing pattern with no change in firing rate during the third week after the lesion compared to normal rats. The systemic administration of m-CPP (20-320 microg/kg, i.v.) dose-dependently increased the firing rate of subthalamic neurons, and the local application of m-CPP, 4 microg, in the subthalamic nucleus also increased the firing rate of subthalamic neurons in the lesioned rats. Similarly, at the same doses, the systemic and local administration of m-CPP induced the excitatory effects on subthalamic neurons in normal and sham rats. The excitatory effect of m-CPP was reversed by the subsequent administration of SB242084 (200 microg/kg, i.v.). These results suggest that the response of subthalamic neurons to 5-HT(2C) receptor stimulation is not altered after 6-hydroxydopamine lesions of the substantia nigra pars compacta.