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BACKGROUND AND AIMS: The subthalamic nucleus (STN) is the best target for deep brain stimulation (DBS) elevating motor symptoms in Parkinson’s disease (PD) patients. Although DBS is beneficial for patients with PD, it can also cause psychiatric and autonomic side effects of unknown etiology. Since the depression-like behavior is described after high frequency subthalamic stimulation (HFS-STN) in rats, it is important to examine impact of HFS-STN on hypothalamic-adrenal axis (HPA) activation and plasma proinflammatory cytokine levels. The aim of this study was to investigate the plasma corticosterone (CORT), TNF-α, IFN-γ and IL-6 levels following HFS-STN in hemiparkinsonian rats. METHODS: Unilateral, continuous HFS-STN (pulse width: 60 µs, frequency: 130 Hz, stimulation intensity: 30–115 µA, during 1 h. stimulation period) was provide in freely moving hemiparkinsonian rats. The model of PD was obtained by stereotactic microinjection of 6-hydroxydopamine into the right substantia nigra pars compacta. The blood samples were collected by heart puncture after the electrical or sham stimulation. The CORT level in plasma was measured by radioimmunoassay method, while concentrations of cytokines were quantified using ELISA method. RESULTS: We found that HFS-STN applied in hemiparkinsonian rats significantly increase plasma CORT level (t27=2.31, P≤0.05) in comparison to SHAM control group). We also observed an increase in IFN–γ (t27=2.89, P≤0.01) and TNF-α (t27=2.88, P≤0.01) concentrations, while the IL-6 level decrease (t27=3.38, P≤0.01) following HFS-STN. CONCLUSIONS: These data shows that HFS-STN influence endocrine and immune parameters in peripheral blood in hemiparkinsonian rats. One hour, continuous HFS-STN activated HPA axis (measured by plasma corticosterone level) and elevated concentrations of pro-inflammatory cytokines. Our results suggest that HFSSTN provokes peripheral immune and endocrine effects similar to observed in behavioral depression.