Cocaine seeking and consumption are oppositely regulated by mesolimbic dopamine in male rats
Year: 2025
Type: article
Abstract: Drug-associated stimuli (cues) can usurp potent control of behavior in individuals with substance use disorders; and these effects are often attributed to altered dopamine transmission. However, there is much debate over the way in which dopamine signaling changes over the course of chronic drug use. Here, we carried out longitudinal recording and manipulation of cue-evoked dopamine release in the core of the nucleus accumbens across phases of substance use in male rats. We show that, in a subset of individuals that exhibit increased cue reactivity and escalated drug consumption, this signaling undergoes diametrically opposed changes in amplitude, determined by the context in which the cue was presented. Dopamine evoked by non-contingent cue presentation (independent of the animal's actions) increases over drug use, producing greater cue reactivity; whereas dopamine evoked by contingent cue presentation (dependent on the animal's actions) decreases over drug use, producing escalation of drug consumption. Therefore, despite being in opposite directions, these dopamine trajectories each promote cardinal features of substance use disorders.
Source: Nature Communications
Institutions: University of Washington, University of Oxford, Charles River Laboratories (United States), National Institutes of Health, National Institute on Drug Abuse, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam University Medical Centers, University of Amsterdam
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1291810785, G1296675194, G1925260111, G259607607, Diametric changes in phasic dopamine to contingent and non-contingent drug cues in the regulation of drug taking and drug seeking, G4248508399, G5386411763, G5847796888, Neural mechanisms regulating cocaine consumption, Training in the Molecular Pharmacology of Abused Drugs, G8071786823, Neuromodulatory mechanisms mediating escalation of drug consumption, G8320436600, G9000219931, Isolation of brain reward circuits using peptidergic systems, University of Washington Center of Excellence in Opioid Addiction Research
OpenAlex ID: W4416142663