Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts

Milan D Valyear,Ivan Trujillo-Pisanty,Iulia Glovaci,Nadia Chaudhri,Soraya Lahlou,Audrey Zaari,C Andrew Chapman

doi:10.1038/s41467-020-17543-4

Milan D Valyear, Ivan Trujillo-Pisanty + Show 5 more

Open Access

https://doi.org/10.1038/s41467-020-17543-4

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Journal: Nature Communications	Publication Date: Jul 28, 2020
Citations: 30	License type: open-access

Affiliation: Concordia University

Abstract

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context.

Highlights

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder
Conditioned approach and entry into a fluid port triggered by a discrete conditioned stimulus (CS) that predicted alcohol (i.e., CS-triggered alcoholseeking) is significantly elevated in a context associated with prior alcohol intake, relative to a familiar, neutral context where alcohol was never consumed[19,20,21]
To determine if this effect was transient or persistent, we examined CS-triggered alcohol-seeking in an alcohol context and a neutral context across multiple sessions without alcohol delivery

Summary

Introduction

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. In support of this idea, preclinical studies show that contexts associated with drug availability can trigger relapse-like renewal of extinguished drug-seeking behaviour[5,6,7] These data bolster a critical role for context in substance use disorders[8], and extend a central hypothesis in the addiction field, which is that environmental stimuli can prompt drug-seeking, -taking and relapse[3,9,10]. This hypothesis originated in studies on the incentive and motivational properties of discrete drug-predictive cues, which in humans are environmental stimuli that occur in close temporal proximity with drug use (e.g., smell or taste of alcohol). The dopamine system is engaged by context, as context can modulate how ventral tegmental area (VTA) dopamine neurons fire in response to discrete cues[27]

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