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Journal of Neuroscience
Article . 2020 . Peer-reviewed
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The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking

Authors: Yu Liu; Philip Jean-Richard-dit-Bressel; Joanna Oi-Yue Yau; Alexandra Willing; Asheeta A. Prasad; John M. Power; Simon Killcross; +2 Authors

The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking

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 self-administration, extinction, and relapse. Our results show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures are unique for different forms of relapse.SIGNIFICANCE STATEMENT It is axiomatic that the actions of dopamine are critical to drug addiction. Yet how relapse to drug-seeking is assembled from activity across the mesolimbic dopamine system is poorly understood. Here we show how relapse to alcohol-seeking relates to activity in specific VTA and accumbens compartments, how these change for different forms of relapse, and how relapse-associated activity relates to activity during self-administration and extinction. We report the mesolimbic dopamine activity signatures for relapse and show that these signatures are unique for different forms of relapse.

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Keywords

Male, Ethanol, Tyrosine 3-Monooxygenase, Dopamine, Dopaminergic Neurons, Drug-Seeking Behavior, Ventral Tegmental Area, Nucleus Accumbens, Membrane Potentials, Behavior, Addictive, Optogenetics, Recurrence, Animals, Conditioning, Operant, Rats, Long-Evans

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    48
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
48
Top 1%
Top 10%
Top 1%
bronze