Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity.
BACKGROUND
Privileged episodic encoding of an aversive event often comes at a cost of neutral events flanking the aversive event, resulting in decreased episodic memory for these neutral events. This peri-emotional amnesia is amygdala-dependent and varies as a function of norepinephrine activity. However, less is known about the amnesiogenic potential of cortisol.


OBJECTIVE
We used a strategy of pharmacologically potentiating cortisol and norepinephrine activity to probe the putative neurochemical substrates of peri-emotional amnesia.


METHODS
Fifty-four healthy individuals participated in a randomized double-blind placebo-controlled study. Within the experimental context of an established peri-emotional amnesia paradigm, we tested the amnesiogenic potential of hydrocortisone (30 mg p.o.) in the presence or absence of the norepinephrine-reuptake inhibitor reboxetine (4 mg p.o.).


RESULTS
Under dual challenge conditions, we observed a linear dose-response relationship in the magnitude and duration of emotion-induced retrograde amnesia.


CONCLUSIONS
Our results are consistent with a phenotypic expression of retrograde amnesia varying as a function of norepinephrine and cortisol coactivation during episodic encoding of aversive events. Our study demonstrates that the adverse cognitive and behavioral sequelae of aversive emotion can be experimentally modeled by a pharmacological manipulation of its putative neurochemical substrates.
Hurlemann
René
R
Department of Psychiatry, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. renehurlemann@gmx.de
Matusch
Andreas
A
Hawellek
Barbara
B
Klingmuller
Dietrich
D
Kolsch
Heike
H
Maier
Wolfgang
W
Dolan
Raymond J
RJ
D000284:Administration, Oral; D000328:Adult; D000648:Amnesia, Retrograde / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007785:Lactose / Q000008:administration & dosage; D008297:Male; D008954:Models, Biological; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism*; D000077593:Reboxetine; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000150:complications*
D000928:Antidepressive Agents; D005938:Glucocorticoids; D009025:Morpholines; D000077593:Reboxetine; D007785:Lactose; D006854:Hydrocortisone; D009638:Norepinephrine