BACKGROUND: Some investigations have demonstrated that exogenous 5-hydroxytryptamine increases the spontaneous firing rate of subthalamic nucleus (STN) neurons in the rat brain.OBJECTIVE: To validate the effect of electrical stimulation to the dorsal raphe nucleus (DRN) on the neu-ronal activities of the STN in rats, as well as analyze the differences in the effects of electrical stimulation at various frequencies.DESIGN, TIME AND SETTING: Experiments were performed from March 2007 to June 2007 in the Electrophysiology Laboratory of Liaoning Medical University with a randomized controlled animal study design.MATERIALS: Twenty-four healthy male Sprague-Dawley (SD) rats, weighing 250-350 g, were selected for this study. An A320R constant electrical stimulator was purchased from World Precision Instruments Com-pany (USA); a Spike 2 biological signal acquisition system was purchased from British CED Company. METHODS: Twenty-four SD rats were randomly assigned into a model group and a normal group, with 12 rats in each group. To mimic Parkinsons disease, rats in the model group were injected with 4 μL of 6-hydroxydopamine into the right striatum, then received deep brain stimulation. Rats in the normal group re-ceived deep brain stimulation in same brain region without modeling. Electrical stimulation (width, 0.06 ms; intensity, 0.2-0.6 mA; frequency, 20-130 Hz; train duration, 5 seconds) was delivered to the DRN. MAIN OUTCOME MEASURES: The firing rates of STN neurons were observed by extracellular record-ing using a biological signal acquisition system. RESULTS: DRN-high-frequency stimulation (DRN-HFS) induced excitation in 59% of the STN neurons in the normal group and 50% of the STN neurons in the model group; mean firing rates increased significantly from (7.14± 0.75) and (7.94 ± 0.61) Hz to (11.17 ± 1.49) and (12.11 ± 1.05) Hz, respectively (P < 0.01). Spontaneous firing rate increased significantly in 53% of neurons in normal rats in a frequency-dependent manner when stimulation frequency was in the range 80-130 Hz.CONCLUSION: DRN-HFS induced an excitatory effect on the spontaneous activity of STN neurons in both normal and PD rats. There was a frequency-dependent effect of electrical stimulation of the DRN on sponta-neous firing activities in STN neurons.