The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Yu LiuGavan P McNally

Abstract

The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking in male rats are assembled from activity across the VTA and the nucleus accumbens. First, we used chemogenetic approaches to show a causal role for VTA TH neurons in two forms of relapse to alcohol-seeking: renewal (context-induced reinstatement) and reacquisition. Then, using gCaMP fiber photometry of VTA TH neurons, we identified medial and lateral VTA TH neuron activity profiles during self-administration, renewal, and reacquisition. Next, we used optogenetic inhibition of VTA TH neurons to show distinct causal roles for VTA subregions in distinct forms of relapse. We then used dLight fiber photometry to measure dopamine binding across the ventral striatum (medial accumbens shell, accumbens core, lateral accumbens shell) and showed complex and heterogeneous profiles of dopamine binding during self-administration and relapse. Finally, we used representational similarity analysis to identify mesolimbic dopamine signatures of s...Continue Reading

Citations

Jun 20, 2020·British Journal of Pharmacology·Asheeta A Prasad, Gavan P McNally
Nov 1, 2020·International Journal of Molecular Sciences·Marie A LabouesseTommaso Patriarchi
Jan 25, 2021·Journal of Neurochemistry·Yu Liu, Gavan P McNally
Sep 25, 2020·Physiological Reviews·Mark E BoutonGavan P McNally
Apr 11, 2021·Physiology & Behavior·Elizabeth G Mietlicki-BaaseDerek Daniels

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