Despite the benefit high frequency stimulation (HFS) of the subthalamic nucleus (STN) has on motor symptoms of Parkinson's Disease (PD), accumulating data also suggest effects of STN-HFS on non-motor behavior. This may be related to the involvement of the STN in the limbic basal ganglia-thalamocortical loops. In the present study we investigated the effect of acute STN-HFS on neurotransmission in associated structures of these pathways, i.e. the nucleus accumbens (NAc) core and shell as well as the ventral tegmental area (VTA) using in vivo microdialysis. Experiments were performed in anaesthetized naive rats and rats selectively lesioned in the substantia nigra pars compacta (SNc) or VTA. We demonstrate that: 1. STN-HFS leads to an increase in DA in the NAc, 2., these effects are more pronounced in the NAc shell than in the NAc core, 3. STN-HFS leads to a decrease in GABA in the VTA, 4. preceding lesion of the SNc does not seem to affect the effect of STN-HFS on accumbal DA transmission whereas 5. preceding lesion of the VTA seems to prohibit further detection of DA in the NAc. We conclude that STN-HFS significantly affects neurotransmission in the limbic system, which might contribute to explain the non-motor effects of STN-HFS.