Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala
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Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala. / Mueller, Madeleine; Fadai, Tahmine; Rauh, Jonas; Haaker, Jan.
in: TRANSL PSYCHIAT, Jahrgang 14, Nr. 1, 03.08.2024, S. 319.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nicotine reduces discrimination between threat and safety in the hippocampus, nucleus accumbens and amygdala
AU - Mueller, Madeleine
AU - Fadai, Tahmine
AU - Rauh, Jonas
AU - Haaker, Jan
N1 - © 2024. The Author(s).
PY - 2024/8/3
Y1 - 2024/8/3
N2 - 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.
AB - 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.
KW - Humans
KW - Nicotine/pharmacology
KW - Nucleus Accumbens/drug effects
KW - Male
KW - Hippocampus/drug effects
KW - Fear/drug effects
KW - Magnetic Resonance Imaging
KW - Adult
KW - Amygdala/drug effects
KW - Female
KW - Young Adult
KW - Double-Blind Method
KW - Discrimination, Psychological/drug effects
KW - Nicotinic Agonists/pharmacology
KW - Extinction, Psychological/drug effects
U2 - 10.1038/s41398-024-03040-5
DO - 10.1038/s41398-024-03040-5
M3 - SCORING: Journal article
C2 - 39097609
VL - 14
SP - 319
JO - TRANSL PSYCHIAT
JF - TRANSL PSYCHIAT
SN - 2158-3188
IS - 1
ER -
