Dopaminergic Control of the Neurotransmitter Release in the Subthalamic Nucleus: Implications for Parkinson’s Disease Treatment Strategies

A critical role of the subthalamic nucleus (STN) in the control of movement has been proposed based on the observations that its lesion or high-frequency stimulation, aimed at altering its activity, is effective in alleviating clinical features of Parkinson’s disease (Bergman et al,. 1990; Bennazouz et al., 1993; Pollak et al., 1993, Benazzouz et al., 2000). Indeed, overactivity of the subthalamic neurons due to the loss of midbrain dopaminergic neurons is believed to be a key feature in Parkinson’s disease. Several studies indicate that the activity of STN neurons can be influenced directly by dopamine and its receptor agonists/antagonists. Indeed, the STN receives a direct dopaminergic input arising in the substantia nigra pars compacta (SNc) and both dopamine D1and D2-like receptors are present in the STN (Canteras et al., 1990; Hassani et al., 1997; Flores et al., 1999). Understanding the position of the STN within the basal ganglia and the possible direct effects of dopamine and its ligands at the level of this nucleus in normal and parkinsonian states may be important in the development of new therapies for Parkinson’s disease. The purpose of this chapter is to give an overview of the current position of the STN in the basal ganglia motorloop and to clarify the role of dopamine at the level of the STN in both normal conditions and in parkinsonian experimental animal models.