Low-intensity Focused Ultrasound For Site-specific Inhibition of Stimulated Dopamine Release

Description:
Dopamine is a neurotransmitter that functions in the brain’s reward system, and dopamine dysfunction is implicated in diseases such as addiction. Many excitatory and inhibitory dopamine drugs are used in current addiction treatments. However, these drugs are not site-specific since dopaminergic neurons are widely distributed in the brain. Low-intensity focused ultrasound (LIFU) neuromodulation has been shown to downregulate dopamine in Parkinson’s disease treatment. However, the mechanism of action for LIFU is not well understood, as real-time dopamine measurement has not been used to study ultrasound neuromodulation. Fast-scan cyclic voltammetry (FSCV) is an electrochemical method used to measure neurotransmitters at high temporal resolution. Here, FSCV is used to study site-specific LIFU inhibition of dopamine. Dopamine is stimulated in the ventral tegmental area and measured in the accumbens core. We observed a 50% inhibition of dopamine after a 2-minute (2 ms burst) low-intensity focused-ultrasound transduction at the medial prefrontal cortex, and this inhibition continues for stimulations up to 1 hour after LIFU treatment. We will vary the LIFU parameters to determine how they affect dopamine release. This fast, site-specific, non-invasive treatment is a promising tool for regulating dopamine and could be used to downregulate dopamine in addicted animals in the future.