Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation

Nicotine addiction develops after prolonged drug use and escalation of drug intake. However, because of difficulties in demonstrating escalation of nicotine use in rats, its underlying neuroadaptations still remain poorly understood. Here we report that access to unusually high doses of nicotine (i....

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Published in:Neuropsychopharmacology 2023-05, Vol.48 (6), p.887-896
Main Authors: Abarkan, Myriam, Fois, Giulia R, Vouillac-Mendoza, Caroline, Ahmed, Serge H, Guillem, Karine
Format: Article
Language:English
Subjects:
Addictions
Animals
Catheters
Cocaine
Drug addiction
Drug dosages
Drug self-administration
Drug use
Experiments
Heroin
Laboratory animals
Life Sciences
Light
Methamphetamine
Neurons
Neurons and Cognition
Nicotine
Nicotine - pharmacology
Prefrontal Cortex
Psychology and behavior
Rats
Reinforcement schedules
Self Administration
Tobacco
Tobacco Use Disorder
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Summary:Nicotine addiction develops after prolonged drug use and escalation of drug intake. However, because of difficulties in demonstrating escalation of nicotine use in rats, its underlying neuroadaptations still remain poorly understood. Here we report that access to unusually high doses of nicotine (i.e., from 30 µg to 240 µg/kg/injection) for self-administration precipitated a rapid and robust escalation of nicotine intake and increased the motivation for the drug in rats. This nicotine intake escalation also induced long-lasting changes in vmPFC neuronal activity both before and during nicotine self-administration. Specifically, after escalation of nicotine intake, basal vmPFC neuronal activity increased above pre-escalation and control activity levels, while ongoing nicotine self-administration restored these neuronal changes. Finally, simulation of the restoring effects of nicotine with in vivo optogenetic inhibition of vmPFC neurons caused a selective de-escalation of nicotine self-administration.
ISSN:0893-133X
1740-634X
0007-0920
DOI:10.1038/s41386-022-01428-9