| April 1, 2004
Norepinephrine Important in Retrieving
(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine have found
that the neurotransmitter norepinephrine is essential
in retrieving certain types of memories. This represents
the first description of a molecule implicated in recalling
memories as opposed to laying down new memories. Teasing
apart different components of this pathway may help
physicians better understand post-traumatic stress disorder
(PTSD) and depression -- both of which involve alterations
in memory retrieval, says lead author Steven
A. Thomas, MD, PhD, Assistant Professor of
Pharmacology. The findings of this research appear in
the April 2 issue of Cell.
Using mutant mice lacking norepinephrine and rats treated
with drugs that block some norepinephrine receptors
(beta blockers), the research team found that this neurotransmitter
is critical for retrieving intermediate-term contextual
and spatial memories, but not for the formation or long-term
consolidation of emotional memories, as previously hypothesized
Mice and rats went through learning tasks that employ
different brain regions: the hippocampus, which governs
spatial and contextual memories; and the amygdala, which
is important for emotional learning and memory in general.
The results of their tests ran counter to currently
held hypotheses that suggest that stress hormones like
norepinephrine are responsible for enhanced memory formation
during emotionally arousing times. “Indeed, we
set out to test that hypothesis with our norepinephrine-deficient
mice,” says Thomas. “We expected to see
a difference in amygdala-dependent behaviors between
the mutants and controls if it were emotional memory,
in general, that was being affected by the absence of
norepinephrine. But we didn’t see that. Instead,
we found a specific impairment in hippocampus-dependent
contextual memory retrieval.”
Using rats given beta blockers and a swimming navigation
task in a water maze, which relies on the hippocampus
but not the amygdala, the researchers sought to determine
if norepinephrine was also necessary for spatial memories.
The tests indicated that norepinephrine is critical
for a period of time after a memory is formed, but is
not critical in recalling older memories. “There
are probably other mechanisms important for retrieving
memories for the longer term that are independent of
norepinephrine,” says Thomas.
This line of research may have relevance to human learning
and memory. Patients suffering from post-traumatic stress
disorder have recurrent intrusive memories; that is,
they experience traumatic events from the past in their
minds. Evidence from studies in other labs suggests
that in PTSD there might be hyper-signaling by norepinephrine.
“Perhaps that’s one reason why PTSD patients
experience these recurrent intrusive memories,”
Depression may include the opposite problem in that
there’s often difficulty in memory retrieval,
and this could be due, in part, to dysfunction of the
adrenergic system. In addition, beta-blockers, which
are used to treat heart failure and hypertension (among
other ailments) block the same norepinephrine receptors
important for memory retrieval. Therefore, when treating
heart disease, the use of beta blockers that do not
cross into the brain may help to avoid memory-related
side effects, suggest the researchers.
Other Penn researchers collaborating on this work are Charles F. Murchison,
Xiao-Yan Zhang, Wei-Ping Zhang, Ming Ouyang, and Anee Lee. The research was supported
in part by grants from the National Institutes of Health, the National Alliance
for Research on Schizophrenia and Depression, and the Mental Retardation and Developmental
Disabilities Research Center at the Children’s Hospital of Philadelphia.
The authors have no competing financial interest in this work.
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