Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear

Matthias F.J. Sperl, Christian Panitz, Nadine Skoluda, Urs M. Nater, Diego A. Pizzagalli, Christiane Hermann, Erik M. Mueller

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.

Forschungsplattform The Stress of Life - Processes and Mechanisms underlying Everyday Life Stress, Institut für Klinische und Gesundheitspsychologie
Externe Organisation(en)
Philipps Universität Marburg, Justus-Liebig-Universität Gießen (JLU), Harvard University
International Journal of Neuropsychopharmacology
Anzahl der Seiten
ÖFOS 2012
501010 Klinische Psychologie
ASJC Scopus Sachgebiete
Psychiatry and Mental health, Pharmacology (medical), Pharmacology
Ziele für nachhaltige Entwicklung
SDG 3 – Gesundheit und Wohlergehen
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