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Brief Report

Relationship of Enhanced Norepinephrine Activity

During Memory Consolidation to Enhanced Long-TermMemory in Humans

Steven M. Southwick, M.D.

Michael Davis, Ph.D.

Beverly Horner, M.A.

Larry Cahill, Ph.D.

Charles A. Morgan III, M.D., M.A.

Paul E. Gold, Ph.D.

J. Douglas Bremner, M.D.

Dennis C. Charney, M.D.

Objective: The purpose of this study was to investigate the ef-

fect of enhanced noradrenergic activity on memory consolida-

tion in humans.

Method: Thirty healthy subjects (21 men and nine women)viewed a series of 12 slides that depicted an emotionally arous-

ing story. Five minutes after viewing the slides, subject

either intravenous yohimbine or intravenous placebo

ble-blind randomized fashion. Multiple blood sam

drawn for determining plasma free 3-methoxy-4-hy

nylglycol (MHPG). One week later subjects took a surp

ory test for the slides.

Results: There was no significant difference in mem

between yohimbine and placebo groups. Linear regr

vealed a significant effect of MHPG on memory sco

group as a whole (subjects who had received yohim

those who had received placebo) and for the place

alone.

Conclusions: These findings strengthen support fo

pothesis that enhanced memory for emotionally

events in humans depends critically on postlearning amodulation.

(Am J Psychiatry 2002; 159:1

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BRIE

placebo group (mean=0.63 ng/ml, SD=0.37) (t=3.21, df=

26.8, p=0.005, unequal variances). The range of MHPG

change values in the yohimbine group (0.22 to 3.27 ng/ml)

was also greater than the range in the placebo group (0.02

to 1.11 ng/ml). Seven of the subjects who received yohim-bine had a peak change in MHPG (range=0.22 to 1.10 ng/

ml) that was no greater than the peak change observed for

each of the 15 subjects who received placebo. That is, for

these seven subjects, yohimbine was no more effective than

placebo in releasing plasma norepinephrine and MHPG.

Memory recall did not differ significantly between the

yohimbine group (mean=0.58, SD=0.06) and the placebo

group (mean=0.56, SD=0.09) (t=1.01, df=25.1, p=0.32, un-

equal variances). However, the seven yohimbine subjects

with the highest peak increases in MHPG (peak changes in

MHPG that were greater than those observed in all 15 pla-

cebo subjects) had a significantly higher mean memory

score than the seven yohimbine subjects with the lowest

peak increases in MHPG (peak changes in MHPG that

were no greater than those observed in any of the 15 pla-

cebo subjects) (t=2.22, df=12, p

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BRIEF REPORTS

two separate stories (one followed by yohimbine and one

followed by placebo), and inclusion of other neuromodu-

lators known to affect memory consolidation, such as epi-

nephrine and glucose.

The present study suggests that enhanced memory inhumans is associated with elevated norepinephrine activ-

ity during memory consolidation. It has been proposed

that enhanced memory for arousing events has signifi-

cance for survival and that catecholamine-mediated en-

hancement of memory consolidation for arousing and

traumatic events may play a role in the reexperiencing

symptoms of posttraumatic stress disorder (7).

Received April 10, 2001; revisions received Oct. 29, 2001, andMarch 18, 2002; accepted March 28, 2002. From the Department of

Psychiatry, Yale University School of Medicine; the Department of

Psychiatry, VA Connecticut Medical Center; the Clinical Neuroscience

Division, National Center for PTSD, West Haven, Conn.; the Depart-

ment of Psychiatry and Behavioral Sciences, Emory University, At-

lanta; the Center for the Neurobiology of Learning and Memory and

the Department of Neurobiology and Behavior, University of Califor-

nia, Irvine; and the Department of Psychology, University of Illinois,

Chicago. Address reprint requests to Dr. Southwick, Department of

Psychiatry (116A), VA Connecticut Medical Center, 950 Campbell Ave.,

West Haven, CT 06516; Steven.Southwick@med.va.gov (e-mail).

Supported by a VA grant.

The authors thank William Mangene, Jeremy Cordov

Rosenberg, and Ralitza Gueroguieda for valuable contribu

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