Focused Ultrasound Modulates Dopamine in a Mesolimbic Reward Circuit

Dopamine is a neurotransmitter that plays a significant role in reward and motivation. Dysfunction in the mesolimbic dopamine pathway has been linked to a variety of psychiatric disorders, including addiction. Low-intensity focused ultrasound (LIFU) has demonstrated effects on brain activity, but how LIFU affects dopamine neurotransmission is not known. Here, we applied three different intensities (6.5, 13, and 26 W/cm ² I _sppa ) of 2-minute LIFU to the prelimbic region (PLC) and measured dopamine in the nucleus accumbens (NAc) core using fast-scan cyclic voltammetry. Two minutes of LIFU sonication at 13 W/cm ² to the PLC significantly reduced dopamine release by ∼ 50% for up to 2 hours. However, double the intensity (26 W/cm ² ) resulted in less inhibition (∼30%), and half the intensity (6.5 W/cm ² ) did not result in any inhibition of dopamine. Anatomical controls applying LIFU to the primary somatosensory cortex did not change NAc core dopamine, and applying LIFU to the PLC did not affect dopamine release in the caudate or NAc shell. Histological evaluations showed no evidence of cell damage or death. Modeling of temperature rise demonstrates a maximum temperature change of 0.5°C with 13 W/cm ² , suggesting that modulation is not due to thermal mechanisms. These studies show that LIFU at a moderate intensity provides a noninvasive, high spatial resolution means to modulate specific mesolimbic circuits that could be used in future studies to target and repair pathways that are dysfunctional in addiction and other psychiatric diseases.