(415c) Imaging Dopamine Signaling Aberrations in Cocaine Sensitized Animals with Near-Infrared Fluorescent Nanosensors

Cocaine locomotor sensitization is a well-established model for understanding the physiological effects of cocaine abuse. Previous studies have established a loss of dopamine D2 autoreceptors in striatal tissue as a consequence of locomotor sensitization, yet how these differences in autoreceptor expression affect dopamine signaling remains unclear. Herein, we utilized non-genetically encoded near-infrared fluorescent nanosensors based on carbon nanotubes to image dopamine modulation in acute brain slices. By leveraging dopamine D2 receptor agonists along with the dopamine nanosensor, we developed a method to identify changes in the density of functional D2 autoreceptors and dopamine signaling aberrations that accompany sensitization, at the level of individual dopamine synapses. We apply our method to quantify changes in D2 autoreceptor activity in the nucleus accumbens core in mice after prolonged cocaine exposure. Our preliminary data indicates a decrease in the number of D2 autoreceptors in cocaine sensitized mice, consistent with prior studies, and suggests that cocaine abuse leads to higher levels of dopamine signaling relative to non-cocaine treated mice. Furthermore, we confirmed that dopamine signaling changes by application of D2 receptor agonists are from loss of individual dopamine release sites rather than changes in the quantity of dopamine released, or changes in dopamine reuptake kinetics. Our study provides a route to understand the changes in neuromodulation that underlie the neurobiology of substance abuse.