Differential release of dopamine in the nucleus accumbens evoked by low-versus high-frequency medial prefrontal cortex stimulation

• Published in: Brain stimulation Vol. 11; no. 2; pp. 426 - 434
• Main Authors: Hill, Daniel F., Parent, Kate L., Atcherley, Christopher W., Cowen, Stephen L., Heien, Michael L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2018
• Subjects: Animals; Beta; Deep brain stimulation; Dopamine; Dopamine - metabolism; Electric Stimulation; Electrical stimulation; Evoked Potentials; Fast-scan cyclic voltammetry; Male; Medial prefrontal cortex; Nucleus accumbens; Nucleus Accumbens - metabolism; Nucleus Accumbens - physiology; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiology; Rats; Rats, Sprague-Dawley; FSCV; VTA; Dopamine; CFME; Deep brain stimulation; Electrical stimulation; Beta; Fast-scan cyclic voltammetry; Nucleus accumbens; Medial prefrontal cortex; NAc; mPFC; CV; DBS; LFP; DA
• ISSN: 1935-861X; 1876-4754
• DOI: 10.1016/j.brs.2017.11.010

The medial prefrontal cortex (mPFC) coordinates goal-directed behaviors, which may be mediated through mPFC regulation of dopamine release in the nucleus accumbens (NAc). Furthermore, frequency-specific oscillatory activity between the frontal cortex and downstream structures may facilitate inter-region communication. Although high-frequency (e.g., 60 Hz) mPFC stimulation is known to increase basal dopamine levels in the NAc, little is known about how phasic dopamine release is affected by mPFC stimulation. Understanding the frequency-specific control of phasic dopamine release by mPFC stimulation could elucidate mechanisms by which the mPFC modulates other regions. It could also inform optimization of deep brain stimulation for treatment of neurological disorders.
The goal of this work was to characterize the frequency response of NAc dopamine release resultant from mPFC stimulation. We hypothesized that the magnitude of dopamine release in the NAc would increase with increasing stimulation frequency.
Electrical stimulation of the mPFC of anesthetized rats was delivered at 4–60 Hz and at varying durations while measuring NAc dopamine release with fast-scan cyclic voltammetry.
mPFC stimulation resulted in phasic dopamine release in the NAc. Furthermore, 20 Hz stimulation evoked the largest peak response for stimulation intervals >5 s when compared to higher or lower frequencies.
Activation of the mPFC drives dopamine release in the NAc in a complex frequency- and duration-dependent manner. This has implications for the use of deep brain stimulation treatment of disorders marked by dopaminergic dysregulation, and suggest that mPFC may exert more specialized control over neuromodulator release than previously understood.
•mPFC stimulation evokes phasic dopamine release in the NAc.•Dopamine release is maximal at 10–20 Hz for stimulation durations >5 s.•At short durations (≤5 s), 60 Hz stimulation resulted in maximal dopamine release.•A significant interaction between frequency and duration of stimulation was shown.