Electrical stimulation-evoked dopamine release in the primate striatum

Background: Primate studies demonstrate that high-frequency electrical stimulation (HFS) of the caudate can enhance learning. Importantly, in these studies, stimulation was applied following the execution of behavior and the effect persisted into subsequent trials, suggesting a change in plasticity rather than a momentary facilitation of behavior. Objectives/Methods: Although the mechanism of HFS-enhanced learning is not understood, evidence suggests that dopamine plays a critical role. Therefore, we used in vivo amperometry to evaluate the effects of HFS on striatal dopamine release in the anesthetized primate. While this does not directly examine dopamine during learning, it provides insight with relation to dopamine dynamics during electrical stimulation and specifically between different stimulation parameters and striatal compartments. Results: We demonstrate that HFS results in significantly more dopamine release in the striatum compared to low-frequency stimulation. In addition, electrical stimulation operates differentially on specific neuronal elements, as the parameters for dopamine release are different for the caudate, putamen and medial forebrain bundle. Conclusions: While not direct evidence, these data suggest that HFS evokes significant dopamine release which may play a role in stimulation-enhanced learning. Moreover, these data suggest a means to modulate extracellular dopamine with a high degree of temporal and spatial precision for either research or clinical applications.