Fast-scan cyclic voltammetry for measurement of extracellular dopamine release in response to self-stimulation

Background: The regulation of extracellular dopamine levels in the nucleus accumbens is a critical component of the brain reward system. The development of fast-scan cyclic voltammetry facilitated the measurement of variations in dopamine release over time, correlating with behavioral responses. However, the available data on extracellular dopamine levels in response to self-stimulation are somewhat conflicting.

Aim: To analyze the patterns of dopamine release in the nucleus accumbens that occur in response to the ventral tegmental self-stimulation, as measured by fast-scan cyclic voltammetry.

Methods: Electrodes were implanted into male Wistar rats to induce self-stimulation and monitor extracellular dopamine levels. The release of dopamine was measured telemetrically, while rats were allowed to move freely. Dopamine levels were measured by monitoring its extracellular concentrations in the nucleus accumbens in vivo using fast-scan cyclic voltammetry. The ventral tegmental irritation was maintained on a fixed-ratio one schedule using a rectangular pulse train with a 38° head elevation.

Results: The first head elevation, and consequently the activation of reward stimulation, induced an increase in the signal of fast-scan cyclic voltammetry, which decreased over time. The release of dopamine in response to self-stimulation demonstrated a consistent increase compared to the baseline levels prior to the initiation of the reaction training. A definitive correlation between the amplitude/time of dopamine release and the intensity of the self-stimulation response was not observed. The maximum dopamine concentration in response to the electrical stimulus increased and remained at a higher level for at least 20 subsequent head elevations. However, the hallmarks of exploratory behavior persisted, despite variations in dopamine levels. The release of dopamine in the initial five minutes of the experiment gradually decreased every two minutes. Following a period of prolonged self-stimulation, the release of dopamine decreased at an interval of 0.5 min.

Conclusion: The study findings are consistent with the hypothesis of fluctuations in the emotional continuum that activates the brain reward mechanisms. Dopamine levels have been demonstrated to reflect the regulatory mechanisms underlying approach and avoidance behaviors in response to self-stimulation and may result from the synthesis of an antedating reward (motivational excitement) followed satisfaction after motor activity.