Abstract
BACKGROUND: Hyperconsolidation of aversive associations and poor extinction learning have been hypothesized to be crucial in the acquisition of pathological fear. Previous animal and human research points to the potential role of the catecholaminergic system, particularly noradrenaline and dopamine, in acquiring emotional memories. Here, we investigated in a between-participants design with 3 groups whether the noradrenergic alpha-2 adrenoreceptor antagonist yohimbine and the dopaminergic D2-receptor antagonist sulpiride modulate long-term fear conditioning and extinction in humans. METHODS: Fifty-five healthy male students were recruited. The final sample consisted of n = 51 participants who were explicitly aware of the contingencies between conditioned stimuli (CS) and unconditioned stimuli after fear acquisition. The participants were then randomly assigned to 1 of the 3 groups and received either yohimbine (10 mg, n = 17), sulpiride (200 mg, n = 16), or placebo (n = 18) between fear acquisition and extinction. Recall of conditioned (non-extinguished CS+ vs CS-) and extinguished fear (extinguished CS+ vs CS-) was assessed 1 day later, and a 64-channel electroencephalogram was recorded. RESULTS: The yohimbine group showed increased salivary alpha-amylase activity, confirming a successful manipulation of central noradrenergic release. Elevated fear-conditioned bradycardia and larger differential amplitudes of the N170 and late positive potential components in the event-related brain potential indicated that yohimbine treatment (compared with a placebo and sulpiride) enhanced fear recall during day 2. CONCLUSIONS: These results suggest that yohimbine potentiates cardiac and central electrophysiological signatures of fear memory consolidation. They thereby elucidate the key role of noradrenaline in strengthening the consolidation of conditioned fear associations, which may be a key mechanism in the etiology of fear-related disorders.
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 759–773 |
| Seitenumfang | 15 |
| Fachzeitschrift | International Journal of Neuropsychopharmacology |
| Jahrgang | 25 |
| Ausgabenummer | 9 |
| Frühes Online-Datum | 24 Juni 2022 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - Sept. 2022 |
Fördermittel
WethankAntoniaV.SeligowskiandKerryJ.Ressler(Neurobiology of Fear Laboratory, McLean Hospital, Harvard Medical School, MA, USA) for valuable discussions and feedback on our data. The present study was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) to E.M.M. (grant no. DFG MU3535/2-1). M.F.J.S. received a Research Training Grant from the Society for Psychophysiological Research (SPR) for a 6-month research stay at McLean Hospital, Harvard Medical School (Belmont, MA, USA). Furthermore, M.F.J.S. was supported by the Research Training Group (RTG) 2271 \u201CBreaking Expectations: Expectation Maintenance vs Change in the Context of Expectation Violations,\u201D funded by the DFG (grant no. DFG 290878970-GRK2271, project 6). M.F.J.S. received a Poster Award for this project at the 57th Annual Meeting of the Society for Psychophysiological Research (SPR) in Vienna (Austria). M.F.J.S. and C.P. were also supported by the DFG grant MU3535/2-3, which was awarded to E.M.M. Over the past 3 years, D.A.P. has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Concert Pharmaceuticals, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, and Takeda Pharmaceuticals; honoraria from the Psychonomic Society (for editorial work) and from Alkermes; and research funding from the National Institute of Mental Health (NIMH), the Dana Foundation, the Brain and Behavior Research Foundation, and Millennium Pharmaceuticals for activities unrelated to the current project. In addition, D.A.P. has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and there are no conflicts of interest with the work conducted in this study. All views expressed are solely those of the authors. M.F.J.S., C.P., N.S., U.M.N., C.H., and E.M.M. reported no biomedical financial interests or potential conflicts of interest. M.F.J.S., C.P., C.H., and E.M.M. are members of the Center for Mind, Brain and Behavior (CMBB), a joint research center of the University of Marburg and the University of Giessen at the Research Campus Central Hessen. Open access publishing was supported by the Open Access Publication Fund of the University of Giessen.
ÖFOS 2012
- 501010 Klinische Psychologie
UN SDGs
Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung
