Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala.
Humans
Nicotine
/ pharmacology
Nucleus Accumbens
/ drug effects
Male
Hippocampus
/ drug effects
Fear
/ drug effects
Magnetic Resonance Imaging
Adult
Amygdala
/ drug effects
Female
Young Adult
Double-Blind Method
Discrimination, Psychological
/ drug effects
Nicotinic Agonists
/ pharmacology
Extinction, Psychological
/ drug effects
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
03 Aug 2024
03 Aug 2024
Historique:
received:
11
01
2024
accepted:
26
07
2024
medline:
4
8
2024
pubmed:
4
8
2024
entrez:
3
8
2024
Statut:
epublish
Résumé
Nicotine intake is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in rodents and humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n = 88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to enhanced physiological arousal to learned threats and overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates of adaptive aversive learning in line with the risk for the development of pathological anxiety.
Identifiants
pubmed: 39097609
doi: 10.1038/s41398-024-03040-5
pii: 10.1038/s41398-024-03040-5
doi:
Substances chimiques
Nicotine
6M3C89ZY6R
Nicotinic Agonists
0
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
319Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB 936 (178316478 - C06)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR 289 (422744262 - A06)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 7470/3-1
Informations de copyright
© 2024. The Author(s).
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