Generalized cue reactivity in rat dopamine neurons after opioids.

Autor: Lehmann CM; Department of Psychiatry, University of Pittsburgh, Pittsburgh, 15219, USA., Miller NE; Department of Psychiatry, University of Pittsburgh, Pittsburgh, 15219, USA., Nair VS; Department of Psychiatry, University of Pittsburgh, Pittsburgh, 15219, USA., Costa KM; Department of Psychology, University of Alabama at Birmingham, Birmingham, 35233, USA., Schoenbaum G; National Institute on Drug Abuse, National Institutes of Health, Baltimore, 21224, USA., Moussawi K; Department of Psychiatry, University of Pittsburgh, Pittsburgh, 15219, USA. khaled.moussawi@ucsf.edu.; Department of Neurology, University of California San Francisco, San Francisco, 94158, USA. khaled.moussawi@ucsf.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2025 Jan 02; Vol. 16 (1), pp. 321. Date of Electronic Publication: 2025 Jan 02.
DOI: 10.1038/s41467-024-55504-3
Abstrakt: Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. A widely accepted assumption is that drugs of abuse result in disparate dopamine responses to cues that predict drug vs. natural rewards. The leading hypothesis is that drug-induced dopamine release represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation. However, this hypothesis has not been directly tested. Here, we develop Pavlovian and operant procedures in male rats to measure firing responses within the same dopamine neurons to drug versus natural reward cues, which we find to be similarly enhanced compared to cues predicting natural rewards in drug-naive controls. This enhancement is associated with increased behavioral reactivity to the drug cue, suggesting that dopamine neuronal activity may still be relevant to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting revised models of dopaminergic function in opioid addiction, and provide insights into the neurobiology of cue reactivity with potential implications for relapse prevention.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)
Databáze: MEDLINE
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